NCT05019703Phase 2Recruiting
M.D. Anderson Cancer Center · Dana-Farber Cancer Institute, Boston, Massachusetts
This phase II trial studies the effect of atezolizumab and cabozantinib in treating adolescents and young adults with osteosarcoma that has come back (recurrent) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help to control the osteosarcoma.
Eligibility: 12 Years to · All · * Signed informed consent form
* Age \>= 12 years at time of signing informed consent form
* Ability to comply with the study protocol, in the investigator's judgment
* Histologically confirmed diagnosis of osteosarcoma
* Metastatic or unresectable locally advanced disease
* Patients must have relapsed or become refractory to conventional therapy including some combination of cisplatin, doxorubicin, methotrexate, and/or ifosfamide
* Measurable disease per RECIST version (v)1.1 (Note: Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation)
* Availability of a representative tumor specimen for exploratory biomarker research. Archival samples are permitted if the tumor samples been obtained within 6 months prior to enrollment and the patient has not received intervening therapy
* A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If only 10-14 slides are available, the patient may still be eligible for the study, after principal investigator confirmation has been obtained
* If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening
* Eastern Cooperative Oncology Group (ECOG) of 0, 1 or 2. Use Karnofsky \>= 50 for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
* Body surface area (BSA) \>= 1 m\^2
* Life expectancy \>= 6 months
* Recovery to baseline or =\< grade 1 CTCAE v5 from toxicities related to any prior treatments, unless adverse events (AE\[s\]) are clinically nonsignificant and/or stable on supportive therapy
* Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (1000/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)
* Lymphocyte count \>= 0.5 x 10\^9/L (500/uL) (obtained within 14 days prior to initiation of study treatment)
* Platelet count \>= 100 x 10\^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
* Hemoglobin \>= 90 g/L (9 g/dL) (obtained within 14 days prior to initiation of study treatment)
* Patients may be transfused to meet this criterion
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN) for age (obtained within 14 days prior to initiation of study treatment)
* Alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN) for age, with the following exceptions: patients with documented bone metastases: ALP =\< 5 x ULN (obtained within 14 days prior to initiation of study treatment)
* Serum bilirubin =\< 1.5 x ULN with the following exception: patients with known Gilbert disease: serum bilirubin =\< 3 x ULN (obtained within 14 days prior to initiation of study treatment)
* Creatinine clearance \>= 50 mL/min (adults \> 18 years of age, calculated using the Cockcroft-Gault formula) or \>= 50 mL/min/1.73m\^2 (pediatrics patients age 12 - 17, calculated using the Bedside Schwartz equation) (obtained within 14 days prior to initiation of study treatment)
* Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol), or 24-hour (h) urine protein =\< 1 g (obtained within 14 days prior to initiation of study treatment)
* Serum albumin \>= 20 g/L (2.0 g/dL) (obtained within 14 days prior to initiation of study treatment)
* For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin (aPTT) =\< 1.5 x ULN (obtained within 14 days prior to initiation of study treatment)
* Negative human immunodeficiency virus (HIV) test at screening
* Negative hepatitis B surface antigen (HBsAg) test at screening
* Women of childbearing potential
NCT05269381Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Eligibility: 16 Years to · All · Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.
PHASE I PRE-REGISTRATION, ALL:
* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
* NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
* NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
* Provide written informed consent. For pediatric patients (age 16-17 years):
* Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
* Willing to return to enrolling institution for follow-up
* Willing to provide blood specimens for research
* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
* Anticipated life expectancy \> 6 months
* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).
* The following lab values obtained ≤ 28 days prior to pre-registration:
* Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
* Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
* International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
PHASE I REGISTRATION, ALL:
* Successful sequencing and production of REAL-Neo vaccine
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* ECOG PS 0 or 1
* Anticipated life expectancy \> 6 months
* The following lab values obtained ≤ 14 days prior to registration:
* Hemoglobin ≥ 9.0 g/dl
* ANC ≥ 1500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.5 x ULN
* ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
* PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
* Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
* Provide written informed consent
* Willing to provide blood and tissue sp
NCT06389799Phase 2Recruiting
Lund University Hospital · Oslo University Hospital HF, Oslo
Dedifferentiated liposarcomas (DDLPS) are aggressive soft tissue sarcomas with no effective medical treatment options.
Immunotherapy with checkpoint inhibitors, so-called PD-1 inhibitors, have shown some effect in DDLPS in previous studies. Effect of immunotherapy can be improved by combining it with other types of tumor drugs. Medicines that inhibit signaling via the FGF receptor, so-called FGFR inhibitors, have shown a tumor-slowing effect in DDLPS in early studies. FGFR inhibitors can also induce changes that make the tumor more available to treatment with immunotherapy.
The study aims to investigate whether the combination of an FGFR inhibitor, pemigatinib, with a PD-1 inhibitor, retifanlimab can provide a tumor-slowing effect in patients with advanced DDLPS who have progressed on first-line treatment.
Eligibility: 18 Years to 100 Years · All · Participants will be eligible for the study if all of the following criteria are met:
1. Be 18 years of age or above, on day of signing informed consent.
2. Must be willing and able to provide written informed consent. Written informed consent must be signed and dated before the start of specific protocol procedures.
3. Must be willing and able to conform to and comply with all protocol requirements, including, all scheduled visits, protocol procedures, and the ability to swallow oral tablets.
4. Histologically confirmed DDLPS\*. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization, polymerase chain reaction (PCR) or sequencing-based methods must be available.
5. Have the presence of at least 1 measurable lesion by CT per RECIST v1.1 that is considered non amenable to surgery or other curative treatments or procedures. Tumor lesions located in a previously irradiated area or in an area subjected to other loco-regional therapy are considered measurable if progression has been demonstrated in the lesion.
6. Disease relapse or radiological progression, as determined by the Investigator, within the last 6 months after at least one line of systemic treatment.
a. Patients considered to be medically unfit for chemotherapy, as assessed by the sarcoma centre in charge of the patient's treatment, can be considered for the trial after discussion with the trial steering committee.
7. Be willing to provide tissue by core or excisional biopsy of a tumor lesion at the time points specified in the Trial Flow Chart. Archival tumor tissue can be used instead of pre-treatment biopsy. Biopsy will only be performed if the risk of complication is considered acceptable for the patient.
8. Have a performance status of 0-2 on the ECOG Performance Scale.
9. Patient must have adequate organ function as indicated by laboratory values obtained within 14 days of receiving the first dose of study drug (see study protocol)
10. Female patients of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
11. Female patients of childbearing potential must be willing to use a highly effective method of contraception, for the course of the study through 180 days after the last dose of study medication. Please refer to Section 5.3 for list of highly effective contraception.
12. Male patients must agree to use an highly effective method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy.
NCT06452602Phase 2Recruiting
Tianjin Medical University Cancer Institute and Hospital · Tianjin Cancer Hospital, Tianjin, Tianjin Municipality
This trial is conducted in patients with unresectable locally advanced esophageal squamous cell carcinoma. The investigators plan to enroll 60 patients with unresectable locally advanced esophageal cancer in Tianjin cancer hospital.
After 2 cycles of induction immunochemotherapy, 60 patients with ESCC will be divided into 2 groups (CR+PR group and SD+PD group) according to the efficacy of induction therapy. Patients in the CR+PR group will be treated with the same immunochemotherapy regimen plus concurrent radiotherapy (50.4Gy/1.8Gy/28f) . And immunotherapy will maintain for a maximum of 1 year. Patients in the SD+PD group will be treated with concurrent chemoradiotherapy (Radiotherapy: PTV/PGTV:50.4Gy/59.92Gy/28f and another chemotherapy regimen). Immunotherapy will not used during chemoradiotherapy because of immunotherapy resistance.
The trial can effectively stratify patients by induction immunochemotherapy, and a more appropriate treatment regimen for patients has the potential to further improve PFS and prolong OS in all patients.
Eligibility: 18 Years to 75 Years · All · 1. Volunteered to participate, cooperated with follow-up visits;
2. Aged 18 years or older, both male and female;
3. Histologically confirmed cT1N2-3M0 or cT2-4bN0-3M0 or cT1-4bN0-3M1( supraclavicular lymph node metastasis) locally advanced ESCC (8th AJCC );
4. Clinically staged as II-IVb inoperable locally advanced ESCC(including non-resectable, or with contraindications to or refusal of surgery);
5. ECOG performance status 0 or 1;
6. Presence of measurable and/or non-measurable lesions as defined by RECIST 1.1;
7. Haven't received any previous systemic anti-tumor therapy (including but not limited to systemic chemotherapy, radiotherapy, molecularly targeted drug therapy, immunotherapy, biologic therapy, topical therapy and other investigational therapeutic agents);
8. Provide fresh or archived tumour tissue samples within 6 months (fresh samples preferred) for biomarker analysis (e.g.PD-L1). Sample types are formalin-fixed, paraffin-embedded \[FFPE\] tumour tissue blocks or at least 5 unstained, 3-5 μm thick FFPE tumour tissue sections;
9. Expected survival ≥ 3 months;
10. Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin count ≥9.0 g/dl or ≥5.6 mmol/l;
11. Adequate renal function, defined as creatinine ≤1.5× ULN or measured or calculated creatinine clearance ≥60 mL/min for those with creatinine levels \>1.5× ULN (Calculated from the Cockcroft-Gault formula);
12. Adequate hepatic function, defined as total bilirubin ≤1.5× ULN and ALT/AST/AKP levels ≤2.5× ULN and albumin ≥2.8 g/dl;
13. Adequate coagulation function, defined as INR ≤1.5× ULN and APTT≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as INR is within the therapeutic range;
14. Women of childbearing potential with a negative urine pregnancy test within 3 days before the first administration of the investigational drugs.
15. Documented informed consent.
NCT07211139Phase IIRecruiting
Samsung Medical Center · Samsung Medical Center, Seoul, Seoul
Head and neck squamous cell carcinoma is a heterogeneous cancer with varying prognoses depending on anatomical location and characteristics, and advanced cancers have a poor prognosis. This study aimed to examine changes in the tumor microenvironment and systemic immune system before and after combination therapy with immune checkpoint inhibitors, the standard first-line treatment for head and neck cancer. The rationale for this research and development project is as follows:
1. While immune checkpoint inhibitors have improved survival rates for head and neck cancer patients, they are only effective in approximately 15% of patients. Because biomarkers predicting treatment response have not yet been clearly identified, targeting target patient populations is challenging.
2. While numerous studies have examined the tumor microenvironment in head and neck cancer, no studies have spatially compared dynamic changes before and after immune checkpoint inhibitor treatment using paired tissue and blood biopsies. Therefore, the specific treatment mechanisms remain unclear.
3. Little is known about how changes in the tumor microenvironment are reflected in the peripheral blood, making noninvasive treatment response monitoring difficult.
4. Immune checkpoint inhibitor treatment is known to enhance the efficacy of subsequent taxane-based chemotherapy, but the mechanism remains unknown.
Therefore, we aim to explore biomarkers that predict treatment response to combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in patients with advanced/metastatic head and neck cancer and develop personalized treatment strategies.
Eligibility: 20 Years to · All · * Histologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)
* Received first-line combination therapy with immune checkpoint inhibitor and cytotoxic chemotherapy
* Availability of tumor tissue samples at Samsung Medical Center
* p16 and PD-L1 expression status evaluable within the institution
* Age ≥ 20 years
* Ability to understand the study purpose and provide written informed consent
NCT07676461Phase IIRecruiting
Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo, Bogotá, Bogota D.C.
This is a prospective observational cohort study conducted at Fundación CTIC in Bogotá, Colombia. It characterizes the oral, fecal and intratumoral microbiome of Colombian adults with advanced solid tumors (gastric, colorectal, breast, cervical and head-and-neck cancer) who receive first-line immunotherapy as standard of care, and compares them with healthy volunteers. Using multi-omics (HiFi metagenomics, 16S, tumor RNA-Seq and untargeted metabolomics), the study aims to identify microbial signatures associated with treatment response and survival, building the initial Colombian cohort of a Cancer Microbiome Atlas with Latin American projection.
Eligibility: 18 Years to · All · * Age 18 years or older.
* Histologically confirmed advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer.
* Candidate for first-line immunotherapy per current clinical guidelines.
* Available FFPE tumor block in institutional or reference pathology archive.
* Able to provide saliva and stool samples at V0 and follow-up.
* ECOG performance status within protocol limits; life expectancy over 3 months.
* Cognitive capacity to give informed consent; signed EVA-BIOBANCO and Atlas consents.
Inclusion Criteria (healthy controls)
* No prior cancer diagnosis.
* No active autoimmune disease; no inflammatory bowel disease.
* No antibiotics, invasive dental treatment, immunosuppressants or corticosteroids in the prior 3 months; no severe active periodontal disease.
NCT06029270Phase 2Recruiting
National Cancer Institute (NCI) · Kaiser Permanente Dublin, Dublin, California
This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The usual approach of treatment is initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is finished, patients may continue to receive additional immunotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend the time without the tumor cells growing or spreading longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.
Eligibility: 18 Years to · All · Inclusion Criteria:
* PRIOR TO STEP 1 REGISTRATION:
* Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites. Patients who present with metastatic disease (de novo) at diagnosis are also eligible. For locoregional recurrence, the disease must not be amenable to potentially curative surgery or re-irradiation. Eligible patient must have the following characteristics:
* Tumor showing (histological/cytological) Epstein-Barr encoded ribonucleic acid (EBER)-positivity (e.g., In situ hybridization, immunohistochemistry) or
* A known history of detectable plasma EBV DNA (via a polymerase chain reaction \[PCR\]-based assay) at any time point since the initial diagnosis of NPC.
* Measurable disease as defined by RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression after the prior radiation therapy has been demonstrated.
* Contrast enhanced CT scan of the chest. The contrast enhanced CT component of a whole-body PET-CT is also acceptable. The plain (non-contrast) CT component of a PET-CT is not acceptable.
* CT the abdomen and pelvis, if clinically indicated (diagnostic quality with contrast, unless contraindicated).
* Patients with known locoregional disease must have contrast enhanced MRI or CT of the nasopharynx and neck as this disease site(s) may be assessed as target lesions. For patients without known locoregional disease, imaging of the nasopharynx and neck is optional.
* Symptomatic and active brain metastases and/or leptomeningeal metastasis on CT and/or MRI imaging: Patients who have prior therapies for brain and leptomeningeal metastasis or cord/cauda compression who are clinically stable for \>= 2 months prior to registration and have discontinued systemic steroids therapy (\> 10 mg/day prednisone or equivalent) \> 4 weeks prior to registration are eligible.
* Patients with base of skull involvement by NPC are allowed unless their disease is directly invading the brain parenchyma, associated with clinical symptoms and/or significant vasogenic edema on radiological imaging.
* Age \>= 18 years.
* Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2.
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
* Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3.
* Platelets \>= 100,000 cells/mm\^3.
* Hemoglobin (Hgb) \>= 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not accepted.).
* Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) or direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN. Patients with known Gilbert's disease who have serum bilirubin level =\< 3 × ULN may be enrolled.
* Alanine transaminase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 × ULN (=\< 5 × ULN for patients with liver metastases).
* Serum creatinine =\< 1.5 × ULN or calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation \>= 30 mL/min for patients with serum creatinine levels \> 1.5 × ULN. Cisplatin or carboplatin may be used at the discretion of the investigator - except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be used instead of cisplatin. CrCl must be \> 50 mL/min for cisplatin to be used.
* Albumin-adjusted calcium level based on corrected calcium equation =\< 1.5 × ULN (patients are allowed to have treatment for hypercalcemia prior to starting treatment).
* No prior systemic treatment of palliative intent for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed. Syste
NCT07607119NARecruiting
Samsung Medical Center · Samsung Medical Center, Seoul, Select Province/State
The purpose of this prospective, single-center, phase II study is to evaluate the clinical efficacy and safety of combining first-line systemic therapy plus immunotherapy with personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR) in patients with unresectable locally advanced gastric cancer.
Eligibility: 19 Years to · All · Age 19 or more years. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Histologically confirmed gastric adenocarcinoma. Tumor biomarker status: HER-2 negative, EBV negative, and Microsatellite Stable (MSS).
Unresectable, locally advanced extent at initial staging (Para-aortic lymph node \[PALN\] and Supraclavicular lymph node \[SCN\] metastases are allowed).
Has completed 3 or more cycles of first-line systemic therapy combined with immunotherapy without evidence of disease progression.
Presence of at least one evaluable lesion according to RECIST v1.1 that is deemed safely irradiable by the investigator.
Voluntary written informed consent provided by the subject.
NCT06901531Phase 3Recruiting
Astellas Pharma Global Development, Inc. · UAB Medicine - UAB Hospital, Birmingham, Alabama
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Zolbetuximab with chemotherapy may be used to treat stomach and GEJ cancer when the cancer cells do not have a protein called HER2 (human epidermal growth factor receptor 2) on their surface (HER2-negative) but do have a protein called Claudin 18.2 (Claudin 18.2-positive). Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. Certain stomach and GEJ cancers may be treated with immunotherapy, which helps the body's immune system fight cancer. This study will give more information about how well zolbetuximab works when given with an immunotherapy medicine called pembrolizumab and chemotherapy. In this study, adults with stomach cancer or GEJ cancer will either be given zolbetuximab with pembrolizumab and chemotherapy or a placebo with pembrolizumab and chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it.
The main aim of the study is to check how long people with stomach cancer and GEJ cancer live after treatment with zolbetuximab with pembrolizumab and chemotherapy compared to placebo with pembrolizumab and chemotherapy.
Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample (biopsy) of their cancer will have the Claudin 18.2 protein, PD-L1 protein, and be HER2-negative. They may have been previously treated with certain standard therapies. People can also take part if they need to take medicines like steroids to suppress their immune system. They cannot take part if they have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with pembrolizumab and chemotherapy, or placebo with pembrolizumab and chemotherapy. People who take part will receive just 1 of the study treatments by chance. The people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in 6-week (42-day) cycles. The study treatment is mainly given to people slowly through a tube into a vein. This is called an infusion. People will receive study treatment as follows: Zolbetuximab or placebo: 1 infusion every 2 or 3 weeks (2 or 3 infusions in a cycle) together with: Chemotherapy (1 of the following types of chemotherapy): 1. CAPOX (capecitabine and oxaliplatin): 1 infusion of oxaliplatin every 3 weeks (2 infusions in a cycle). People will also take 1 tablet of capecitabine twice a day for 2 weeks (14 days) at the start of each cycle (Day 1) and again in the middle of each cycle (Day 22). After 8 study treatments people will receive capecitabine only. 2. Modified FOLFOX6 or mFOLFOX6 (5-fluorouracil, folinic acid and oxaliplatin): 1 infusion every 2 weeks (3 infusions in a cycle). After 12 study treatments people will receive folinic acid and fluorouracil only, instead of mFOLFOX6. Pembrolizumab: 1 infusion every 3 or 6 weeks (1 or 2 infusions in a cycle). People can be in the study and will receive study treatment until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People may receive pembrolizumab for up to 2 years. People will visit the clinic on certain days to receive their study treatment and have health checks. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample if they stop treatment because their cancer has worsened. People will visit the clinic after they stop their study treatment. People will be asked about any medical problems and will have a health check. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.
Eligibility: 18 Years to · All · * Participant has histologically confirmed gastric or Gastroesophageal Junction (GEJ) adenocarcinoma.
* Participant has radiographically confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to randomization.
* Participant has radiologically evaluable disease (measurable and/or nonmeasurable) according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1, ≤ 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
* Participant has Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0 to 1.
* Participant has predicted life expectancy ≥ 12 weeks.
* Participant must be a candidate to receive mFOLFOX6 or CAPOX and pembrolizumab.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of child bearing potential (WOCBP)
* WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview), and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions).
* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final administration of oxaliplatin and for 6 months after final administration of all other study interventions.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period, and for 6 months after final investigational study intervention administration.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final investigational study intervention administration.
* Male participant must not donate sperm during the treatment period and for 6 months after the final investigational study intervention administration
* Participant has a Human Epidermal Growth Factor Receptor 2 (HER2) -negative tumor.
* Participant's tumor expresses Claudin18.2 (CLDN18.2) in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
* Participant's tumor expresses Programmed death ligand (PD-L1) combined positive score (CPS) ≥ 1 as determined by central IHC testing.
* Participants with known microsatellite instability-high or mismatch repair deficient status may enroll as long as they meet the PD-L1 positivity criteria.
* Participant must meet all of the criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In case of multiple central laboratory data within this period, the most recent data should be used.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study.
NCT07676461Phase IIRecruiting
Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo, Bogotá, Bogota D.C.
This is a prospective observational cohort study conducted at Fundación CTIC in Bogotá, Colombia. It characterizes the oral, fecal and intratumoral microbiome of Colombian adults with advanced solid tumors (gastric, colorectal, breast, cervical and head-and-neck cancer) who receive first-line immunotherapy as standard of care, and compares them with healthy volunteers. Using multi-omics (HiFi metagenomics, 16S, tumor RNA-Seq and untargeted metabolomics), the study aims to identify microbial signatures associated with treatment response and survival, building the initial Colombian cohort of a Cancer Microbiome Atlas with Latin American projection.
Eligibility: 18 Years to · All · * Age 18 years or older.
* Histologically confirmed advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer.
* Candidate for first-line immunotherapy per current clinical guidelines.
* Available FFPE tumor block in institutional or reference pathology archive.
* Able to provide saliva and stool samples at V0 and follow-up.
* ECOG performance status within protocol limits; life expectancy over 3 months.
* Cognitive capacity to give informed consent; signed EVA-BIOBANCO and Atlas consents.
Inclusion Criteria (healthy controls)
* No prior cancer diagnosis.
* No active autoimmune disease; no inflammatory bowel disease.
* No antibiotics, invasive dental treatment, immunosuppressants or corticosteroids in the prior 3 months; no severe active periodontal disease.
NCT04850729Phase IIRecruiting
Nanfang Hospital, Southern Medical University · Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong
Perioperative drug treatment has gradually become the standard regimen for locally advanced gastric cancer, whereas only a subset of patients could benefit from it. Therefore, one major challenge for perioperative drug treatment is to construct promising biomarkers and to screen out potential beneficial patients. Recent evidence has revealed that tumor microenvironment (TME) is highly associated with the prognosis of gastric cancer. Meanwhile, tumor microenvironment score (TMEscore) established with transcriptomic data is a robust biomarker for predicting prognosis and guiding individualized immunotherapy strategies. However, its predictive value for perioperative drug treatment outcomes warrants further exploration and validation. The study is a multi-center, observational study to evaluate the relationship between the efficacy of perioperative treatment and tumor microenvironment in patients with locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma, aiming at further determining the predictive value of TMEscore and establishing a comprehensive treatment-efficacy evaluation system for gastric cancer.
Eligibility: 18 Years to 75 Years · All · 1. Histologically or cytologically confirmed locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma at the stage of cT2-T4aNxM0 (AJCC 8th) without distant metastases and without infiltration of adjacent structures and organs.
2. 18-75 years old.
3. Willing to provide residual tumor tissues after routine clinical diagnosis for tumor microenvironment detection analysis.
4. Patients agree to participate in the study and sign the informed consent.
5. Patients need to receive perioperative drug therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
NCT07305428NARecruiting
The University of Hong Kong · Queen Mary Hospital, Hong Kong
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide and ranks the third on the incidence of cancer-related death. There are more than 500000 new cases diagnosed annually worldwide. The incidence and prevalence of HCC are on rising trend with the majority of the disease burden is in Asia where viral hepatitis B is endemic. Surgical resection, radiofrequency ablation (RFA) and liver transplantation (LT) represent the only chance of cure for HCC patients. Despite more aggressive surgical approach has been adopted in most Asian countries, yet curative intervention remains only amendable in 30% of patients. Most patients are diagnosed with intermediate or advanced stage diseases; the long-term cure rate is only 0-10%. Hence, every effort has been made in an attempt to convert inoperable HCC into operable disease (i.e. downstaging) in order to improve the chance of survival of these patients. The current study, to our knowledge, will be the first study in the field to deploy a novel treatment strategy to deploy both immunotherapy and stereotactic beamed radiotherapy to induce tumor shrinkage rendering it become operable cancer.
Eligibility: 18 Years to 80 Years · All · * Diagnosis of HCC is made according to American Association for the Study of Liver Diseases (AASLD) practice guideline 2010: patients with cirrhosis of any etiology and patients with chronic hepatitis B (HBV) who may not have fully developed cirrhosis, the presence of liver nodule \>1cm and demonstrated in a single contrast enhanced dynamic imaging \[either computed tomography (CT) or magnetic resonance imaging (MRI)\] of intense arterial uptake and "washout" in portal venous and delayed phases.
* Tumor size 5-25 cm or number of lesions ≤3 or segmental portal vein involvement
* Age: 18-80 years old
* Child Pugh liver function class A-B7
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
