NCT04273061Phase 2Recruiting
British Columbia Cancer Agency · BC Cancer, Vancouver, British Columbia
This study will investigate the effects of atezolizumab on select cancer types in people whose analysis of tumour DNA and RNA indicates they may be sensitive to atezolizumab. This study aims to determine if the information from the cancer genome analysis corresponds with the effects of atezolizumab on individuals and their cancer.
This is a Phase 2 study, which is undertaken after preliminary safety testing on a drug is completed, and will involve approximately 50 participants. Participants are assigned to one of 3 cohorts based on their primary tumour type: gastrointestinal (GI), sarcoma, and 'other' cancer types. Participants in all cohorts will receive the same dose of atezolizumab (1200 mg every 3 weeks). Participants continue on treatment until they no longer may benefit from the treatment or they decide to stop treatment.
Eligibility: 18 Years to · All · * Age greater than or equal to 18 years at the time of signature of informed consent.
* Participants with an incurable solid tumour who have undergone whole genome and transcriptome analysis (WGTA) as part of Personalized OncoGenomics (POG) or equivalent program.
a. Participants must have had successful sequencing of their tumour, been formally reviewed by the POG (or POG-approved) genome analysts and found to have CAPTIV-8 factors identified (including Immune, Burden, Variant (IBV) score ≥ 5), been reviewed at the Molecular Tumour Board (MTB) (or site equivalent), and allocated to a specific tumour-defined cohort (that is open for enrolment) with a final opinion documented.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Participants must have measurable disease, as defined by RECIST 1.1.
* Life expectancy of at least 12 weeks.
* Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment:
1. Absolute neutrophil count (ANC) ≥ 1500 cells/µL without granulocyte colony- stimulating factor support.
2. White blood cell (WBC) counts \> 2500/µL.
3. Lymphocyte count ≥ 500/µL.
4. Serum albumin ≥ 2.5 g/dL.
5. Platelet count ≥ 100,000/µL without transfusion (without transfusion within 2 weeks of laboratory test used to determine eligibility).
6. Hemoglobin ≥ 9.0 g/dL, participants may be transfused or receive erythropoietic treatment to meet this criterion.
7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × Upper Limit of Normal (ULN). This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation must have an INR or aPTT within therapeutic limits for at least 1 week prior to enrolment.
8. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN with the following exceptions: i) Participants with documented liver metastases: AST and/or ALT ≤ 5 × ULN. ii) Participants with documented liver or bone metastases: ALP ≤ 5 × ULN.
9. Serum bilirubin ≤ 1.5 × ULN. Participants with known Gilbert's syndrome who have serum bilirubin level ≤ 3 × ULN may be enrolled.
10. Serum creatinine ≤ 1.5 × ULN.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than 1% (one percent) per year during the treatment period and for at least 5 months after the last dose of atezolizumab.
* For men: agreement to remain abstinent (refrain from heterosexual intercourse with a female partner of childbearing potential or who is pregnant) or use contraceptive measures that result in a failure rate of less than 1% (one percent) per year, and agreement to refrain from donating sperm, during the treatment period and for at least 5 months after the last dose of atezolizumab.
* Asymptomatic participants with treated or untreated CNS lesions are eligible provided that all of the following criteria are met:
1. Measurable disease, per RECIST 1.1, must be present.
2. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
3. The participant has not undergone stereotactic radiotherapy within 7 days prior to the initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
4. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
* Ability to give informed consent for the study procedures defined in this protocol.
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
NCT04132895Phase IIRecruiting
University College, London · University College Hospitals London NHS Foundation Trust, London, Greater London
There has been little improvement in outcome for patients with osteosarcoma (OS) over the last 20 years. There have been only a few clinical trials of new treatments and no major new therapies introduced recently. This is in part because there is no good understanding of the biology of osteosarcoma, but also trials have only included subgroups of patients. The more that is understood about how and why osteosarcoma arises and grows the better clinicians will be able to decide what treatments are most likely to work best.
The purpose of this project is to collect high quality clinical data about patients of all ages with osteosarcoma, such as information about the size of the disease, how it was diagnosed and where it is at diagnosis, what treatments were given and how the disease responded the treatments.
Blood and tissue samples will also be collected for analysis in research laboratories. By looking at the results of the laboratory findings and the clinical data together, the questions will start to be answered about why osteosarcomas arise and grow, what makes it spread, and why some patients respond to treatment better than others. As time goes on, this information is planned to be used to develop clinical trials of new treatments.
Alongside this, the aim is to find out more about how osteosarcoma and its treatments affect the lives of those living with this disease. This information will help provide the most appropriate care and support that will meet the needs of each patient.
Ultimately, the aim is to improve the care and treatment of osteosarcoma patients so that they may live longer and better lives.
Eligibility: 18 Years and older · All · * New histological diagnosis of osteosarcoma or in the absence of osteoid seen on biopsy, pathology and imaging supportive of a diagnosis of osteosarcoma. (It is well recognised that some patients may present with features suggestive of osteosarcoma (under 40 years, radiological abnormality compatible) but in whom no osteoid is detected in needle biopsy. Although categorised as spindle cell tumour of bone, such patients are usually treated in an identical approach to osteosarcoma. A definite diagnosis of osteosarcoma is then often possible after surgery when the entire resection specimen is available.)
* Written informed consent of patient and/or parent/legal guardian.
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
NCT07089992Phase 2Recruiting
Memorial Sloan Kettering Cancer Center · Memorial Sloan Kettering at Basking Ridge (All Protocol Activities), Basking Ridge, New Jersey
The purpose of the study is to find out if pembrolizumab is a useful treatment that causes few or mild side effects in people with ultra-rare sarcoma. The researchers will also study how the immune system responds to the study treatment.
Pembrolizumab is a type of drug called a PD-1 inhibitor. It is designed to block a protein called programmed cell death protein 1 (PD-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them.
Eligibility: 18 Years to · All · Inclusion:
* Patients must have pathologically confirmed diagnosis of one of the following:
1. Pleomorphic liposarcoma
2. PEComa (perivascular epithelial cell tumor)
3. Epithelioid sarcoma
4. CIC-rearranged sarcoma
5. SEF/LGFMS: Sclerosing epithelioid fibrosarcoma - low grade fibromyxoid sarcoma
* Molecular characterization of the tumor, if available, will be recorded. If no such molecular data are available, note as such.
* Patient should have recurrent or metastatic disease not judged to be curable with other means
* Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy or stop prior therapy due to toxicity or patient choice. The reason for this progression or other reason for changing therapy must be documented, employing tumor measurements when available.
* Definition of Measurable Disease
* Measurable disease as per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions for a minimum of 3 months after completion of such therapy
* Patients with treated brain metastases are eligible if follow up brain imaging after CNS-directed therapy shows no evidence of progression at least 4 weeks after the completion of therapy as shown by follow up imaging before study screening
* One to 3 prior lines of therapy are permitted (including neoadjuvant/adjuvant or metastatic/recurrent disease)
* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible. Patients with alopecia and other toxicities considered clinically nonsignificant and/or stable on supportive therapy, as determined by the investigator, are also permitted on study.
* Administration of killed vaccines is allowed
* Age ≥ 18 years of age.
* ECOG Performance Status 0-1 (Karnofsky 70-100)
* Required organ function (specimens to be collected within 14 days of the start of the study intervention)
* Adequate hematologic function, defined as:
* Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl
* Adequate renal function defined, as:
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert disease who have bilirubin level ≤ 3 x ULN may be enrolled)
* AST and ALT ≤3 x institutional ULN
* Adequate cardiac function, defined as: class II or better New York Heart Association (NYHA) Functional Classification.
* For patients with known HIV, HBV, and/or HCV infection \[HIV, HBV, and HCV testing do not need to be performed as part of the study; the below language provides guidelines for inclusivity of patients with known HIV, HBV, and/or HCV infection\]:
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and CD4+ T cell count of at least 350 cell/mm3 are eligible for this trial.
* HIV-infected patients with a history of either Kaposi sarcoma or Castleman disease are excluded from this study
* HIV-infected patients must not have had an AIDS defining opportunistic infection within the past 12 months
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Exclusion:
* No prior diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
* No
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.
NCT06083883Phase 1Recruiting
M.D. Anderson Cancer Center · MD Anderson Cancer Center, Houston, Texas
The goal of this clinical research study is to find a recommended dose of donated NK cells that can be given along with chemotherapy to patients with advanced cancers. The safety and effects of this therapy will also be studied.
Eligibility: 16 Years to 80 Years · All · 1. Patients with all cancer histology, with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the preenrollment tumor sample, for the dose escalation cohort. NY-ESO expression must be confirmed at MDACC prior to study entry.
2. Patients with histologically confirmed synovial sarcoma (cohort 1) or myxoid/round cell liposarcoma (cohort 2), with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the pre-enrollment tumor sample, for the expansion cohorts. Archival samples will be permitted for screening. NY-ESO expression must be confirmed at MDACC prior to study entry.
3. Patients must meet disease-specific eligibility criteria (see below).
4. Patients must have relapsed or become refractory to standard of care treatment and must have received at least one prior line of systemic therapy including either doxorubicin and/or ifosfamide (synovial sarcoma and MRCLS) or trabectedin (MRCLS).
5. Patients must have measurable disease per the RECIST v1.1 at enrollment.
6. Patients must be at least 2 weeks from last cytotoxic chemotherapy at the time of first administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least 3 days prior to administration of lymphodepleting chemotherapy.
7. Patients must be at least 3 months from any cell therapy for malignancy.
8. Eastern Cooperative Oncology Group performance status 0-1 (Appendix A).
9. Adequate organ function at screening, as defined by the following:
1. Renal: Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥45 ml/min/1.73 m2
2. Hepatic: alanine transaminase (ALT)/aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL or ≤ 3.0 mg/dL for patients with Gilbert's Syndrome. No history of liver cirrhosis and no ascites.
3. Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
4. Pulmonary: No clinically significant pleural effusion (per principal investigator \[PI\] judgement), and baseline oxygen saturation ≥ 92% on room air,
5. Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL
6. Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.
10. Able to provide written informed consent.
11. Aged 16-80 years.
12. Weight ≥40 kg.
13. All male and female patients who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Female patients who become pregnant or suspect pregnancy must immediately notify their doctor. Females patients who become pregnant will be taken off study. Men who are able to have children must use effective birth control while on the study therapy.
Acceptable forms of birth control for male patients include: condom with spermicide or abstinence. If the male patient fathers a child or suspects that
NCT06323239Phase 2Recruiting
Sun Yat-sen University · Sun Yat-sen University Cancer Center, Guangzhou, Guangdong
This is a prospective, single-arm, phase II clinical trial. The purpose of this study is to evaluate the efficacy and adverse effect of SBRT and LDRT combined with programmed death 1 (PD-1) antibody and chemotherapy in recurrent/metastatic nasopharyngeal carcinoma patients.
Eligibility: 18 Years to 75 Years · All · * Diagnosed as recurrence/metastatic NPC
* Histopathological diagnosis of NPC(WHO II/III)
* ECOG 0-1 point
* No treatment to r/mNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
* No contraindications to immunotherapy and chemoradiotherapy;
* At least one lesion could receive SBRT safely;
* Subject must have a measurable target lesion based on RECIST v1.1;
* Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/ L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
* Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
* Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
* Take effective contraceptions during and three months after treatment;
* Patients must be informed of the investigational nature of this study and give written informed consent.
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.
NCT05954702NARecruiting
Instituto do Cancer do Estado de São Paulo · Instituto do Cancer do Estado de São Paulo (ICESP), São Paulo, São Paulo
Esophagectomy has high rates of morbidity and mortality, in many cases due to esophagus reconstruction. Anastomotic leakage and fistula are the main esophagectomy complications. Many studies underwent to investigate the cause for anastomotic leakage after esophagectomy, however none of them conclude it is related to surgery or suture technique. However, it seems to be triggered by the ischemia caused after stomach mobilization to esophagus reconstruction, or even tension in the anastomosis.
Considering the post esophagectomy with gastroplasty high morbidity and mortality rates, strategies to create a new vascularization source and decrease anastomotic leakage rates is important. In this study researchers will evaluate whether a TRAM flap transfer supercharged is effective on decrease morbidity related to anastomosis ischemia in patients undergoing esophagectomy.
Eligibility: 18 Years to · All · * Diagnosis of esophageal malignancy cancer;
* Ability to understand and collaborate during treatment;
NCT05005403Phase 1Recruiting
AbbVie · City of Hope National Medical Center /ID# 276272, Duarte, California
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Eligibility: 18 Years to · All · * Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 0 or 1 and a life expectancy of \>= 3 months.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
* Laboratory values meeting criteria outlined in the protocol
* NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
* HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
* Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
* Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
* High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have \>5 lines of prior therapy.
* Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
* Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
NCT06148077NARecruiting
Universidad de La Frontera · Barbara Burgos Mansilla, Temuco, Cautin
Trismus has been reported as the second most common comorbidity in survivors of head and neck cancer (HNC). It is mainly associated with post-radiotherapy subcutaneous fibrosis, muscular atrophy, damage to neurological structures in the neck, or a combination of all, affecting masticatory musculature. In addition to this, the loss of flexibility and strength in the shoulder has also been shown to be related to deficits in the function and quality of life of these patients.
The goal of this clinical trial is to determinate the effectiveness and safety of Manual Therapy (MT) on Oral Opening, Swallow Function, as well as the mobility of the upper quarter, the strength of cervical musculature, pain, functionality, and the perception of quality of life in head and neck cancer survivors.
Participants will be assigned randomly to the study groups: a) manual therapy program and control motor exercises and b) motor control exercises (usual care).
The assessment refers to a baseline form (at the beginning of the study), at 6 weeks and at 6 weeks of patient follow-up.
Eligibility: 18 Years to · All · * individuals with HNC
* individuals over 18 years of age
* individuals who have undergone oncological surgery of the head and neck and/or radiotherapy
* having finished oncological medical treatment between 3 and 36 months before inclusion
* having a medical diagnosis of trismus and/or TMD and/or cervical or shoulder dysfunction
* Spanish native speakers
