NCT06136884Phase 1Recruiting
A2A Pharmaceuticals Inc. · Karmanos Cancer Institute, Detroit, Michigan
The purpose of this study is to assess the safety, tolerability and efficacy of the study drug AO-252 and identify the best dose for use in future studies.
Eligibility: 18 Years to · All · 1. Adults ≥ 18 years of age.
2. Patient has histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumors with TP53 mutation/loss and with/without brain metastasis. Patients must have relapsed/be refractory to at least 1 line of systemic therapy in the metastatic setting (excluding melanoma).
3. Prostate cancer:
1. mCRPC with histologic confirmation of adenocarcinoma. mCRPC with neuroendocrine features or mixed histology are excluded
2. Patients will be enrolled irrespective of the TP53 status
3. Participant must have prostate specific antigen (PSA) of ≥ 2 ng/mL
4. Is surgically or medically castrated, with testosterone levels of less than 50 ng/dL
5. Patients who progressed on at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), and or at least 1 prior systemic chemotherapy (e.g., docetaxel)
4. Solid tumors with brain metastasis:
1. Histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumors excluding melanoma with TP53 mutation/loss and tumor must have relapsed/be refractory to at least 1 line of systemic therapy. Untreated brain metastases not requiring immediate local CNS therapy
2. Previously treated brain metastases with progression of previous lesions or new lesions, but not requiring immediate local CNS therapy
3. At least one measurable untreated brain lesion ≥0.5 cm and \<3.0 cm in the longest axis
4. Prior SRS radiosurgery (must be completed within 7 days of study treatment initiation) is allowed as long as the previous treatment volume does not overlap with the current targets.
5. Measurable disease per RECIST v1.1 criteria. For mCRPC patients, tumor response will be evaluated using RECIST version 1.1 (soft tissue) and PCWG-3 criteria (bone) and efficacy endpoints will also include radiographic progression-free survival (rPFS), PSA50 response and PSA progression
6. Adequate bone marrow reserve, cardiac, liver, and renal function:
1. Absolute neutrophil count (ANC) ≥ 1,500/mm3
2. Platelet count ≥ 100,000/mm3
3. Hemoglobin ≥ 9 g/dL
4. Bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 × ULN
5. Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present)
6. INR ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy and PT or aPTT is within therapeutic range of intended use of anticoagulants
7. Creatinine clearance ≥ 60 mL/min (by Cockroft Gault formula).
7. Female patients of child-bearing potential must have a negative serum pregnancy test and use at least 1 form of acceptable birth control method listed below as approved by the Investigator before initiating study treatment and for 3 months after the last dose of study drug.
1. Sterilization
2. Any hormonal contraceptives (non-CYP 3A4 inhibitors) associated with inhibition of ovulation
3. IUD (intrauterine device) or intrauterine hormone releasing system
8. Male patients must be sterilized or use a form of barrier contraception, such as condoms with spermicide, during the study and for 3 months after the last dose of study drug.
9. Life expectancy of ≥ 3 months.
10. Ability to provide written informed consent.
11. An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
NCT02390518Phase 1Recruiting
University of Utah · Huntsman Cancer Institute, Salt Lake City, Utah
This is a Phase I dose escalation and expansion trial. The purpose of this study is to determine the maximum tolerated dose of radiation received during stereotactic radiosurgery in patients with brain metastases who have never received radiation to the brain before.
Eligibility: 18 Years to · All · * Clinically confirmed brain metastases by CT or MRI criteria. If there is evidence of extra-cranial metastatic disease, it is preferable that the lesions be pathologically confirmed (see section 4.2.5 for excluded histologies) and reviewed by a University of Utah or Huntsman Cancer Hospital pathologist if the initial review was done at an outside facility.
* Prior brain surgery is allowed, although a lesion situated in the operative bed would not be selected to receive an experimental dose of SRS treatment. SRS should be delivered 4-6 weeks post-surgery if the patient had a craniotomy for resection of a lesion. Enrollment of a patient with the goal of performing SRS outside of the 4-6 post-craniotomy window is at the PI's discretion.
* Patients must have 1-5 untreated brain metastases total.
* For patients planning to enroll in Cohort 1a (including expansion) or Cohort 1b: Tumor volume ≤ 4.1888 cm3 by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. Patients who have at least one additional lesion that is larger than the lesions eligible for the expansion cohort, but who are unable to find another open cohort, will have the eligible lesion(s) treated in the expansion cohort, and the remaining lesion(s) treated at the standard dose.
* For patients enrolling in the expansion Cohort 1a: Up to five brain metastases with tumor volume ≤ 0.5237 cm3 by CT or MRI measurement at the time of consultation/screening will be treated on trial with the MTD. Brain metastases with volume \> 0.5237 cm3 will be treated by standard of care SRS dosing.
* For patients enrolling in Cohort 1b: Tumor volume of \> 0.5237 cm3 and ≤ 4.1888 cm3 by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. All other brain metastases will be treated by standard of care SRS dosing.
* As of Protocol Version 9, Cohorts 2 and 3 are permanently closed to accrual. For patients planning to enroll in Cohort 2 or 3: Equivalent tumor diameter ≤ 40 mm by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. Equivalent tumor diameter \</=40 mm by CT or MRI measurement for all lesions treated by standard of care SRS dosing.
* All metastatic lesions must be separated by a minimum of 3 cm as measured from the peripheral edges of the lesions that are in closest proximity to one another. If multiple lesions are present and are not all ≥ 3 cm away from each other, the patient will be deemed ineligible.
* Prior systemic therapy is allowed, although appropriate washout is required for patients who have been on BRAF inhibitors (at least 7 days).
* For subjects currently on active systemic cancer therapy, the treating medical oncologist should be consulted to ensure proper washout (if appropriate) periods prior to SRS.
* Patients must be at least 18 years of age.
* Karnofsky Performance Status (KPS) ≥ 60.
* Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
* Women of child-bearing potential must have a negative pregnancy test within 10 days of study enrollment and must agree to use an acceptable method of birth control while receiving radiation and for 3 months after radiation. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for \>1 year.
* Men who are able to father a child must agree to use an acceptable method of birth control while receiving radiation, and for 3 months after radiation.
NCT07587957NARecruiting
Florida Atlantic University · Florida Atlantic University, Boca Raton, Florida
The purpose of this study is to assess the feasibility of a 4-week intervention combining exercise and transcranial alternating current stimulation (Ex+tACS) in breast cancer survivors who report experiencing cancer-related cognitive impairment. Feasibility will be assessed by measuring participant retention, adherence, satisfaction with the intervention, and safety. The researchers will also examine pre-to-post intervention changes in attention, executive function, working memory, perceived cognitive function, and physical function before, after, and four weeks post intervention completion in the Ex+tACS group compared to a control group who will receive exercise and a placebo tACS condition (CON).
Eligibility: 18 Years to · All · * Breast cancer survivors (≥18 years) will be eligible to participate if the following inclusion criteria is met:
* Diagnosed non-metastatic breast cancer (stages 0-3)
* Completed primary breast cancer treatment (surgery, chemotherapy, radiation) for at least 3 months
* Self-reported cognitive impairment after cancer treatment
NCT07632092Phase IIRecruiting
Centre Hospitalier Universitaire, Amiens · CHRU Amiens, Amiens
Various treatment options are available for brain metastases, depending on factors such as lesion site or number lesions. Radiotherapy is a commonly used treatment. Following stereotactic radiotherapy for brain metastases, a potential complication, namely brain radionecrosis, can occur subsequently. It is essential to differentiate between this radionecrosis and lesion recurrence in order to determine the appropriate treatment approach. Contrast-enhanced magnetic resonance imaging (MRI) is the most widely used technique for monitoring brain metastases. Therefore, patients undergo routine MRI at 3 months and during subsequent follow-ups, but if the lesion evolve and if distinguishing between recurrence and radionecrosis is challenging, an \[18F\]-FDG PET scan is then prescribed by oncologists or radiotherapists during follow-up consultations. As part of the standard patient management protocol, a 10-minute image acquisition begins after a 45-60 minutes wait following the radiotracer injection. A second image acquisition is then conducted 3-4 hours later. For both acquisitions, a low-dose X-ray scanner is synchronously coupled to allow attenuation correction of the PET images.
Patient for whom a \[18F\]-FDG PET cerebral examination has been prescribed as part of the usual management of brain metastases will be eligible to the protocol. If the patient agrees to participate, an early imaging session is initiated immediately upon radiotracer injection, lasting 15 minutes in addition to the standard acquisition protocol.
Eligibility: 18 Years to · All · * Patient referred for cerebral \[18F\]-FDG PET examination prescribed as part of his usual medical care for brain metastasis.
* Age ≥ 18 years old
* Affiliation to a social security program
* Ability of the subject to understand and express his consent
NCT05124912NARecruiting
Monteris Medical · UCLA, Los Angeles, California
Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.
Eligibility: 18 Years to · All · In order to be eligible to participate in this study, an individual must meet all of the following criteria:
1. Patients with radiographically proven (by gadolinium-enhanced \[Gd-\] MRI) parenchymal brain metastases from histologically confirmed non-central nervous system (CNS) cancer.
2. Patients with a "targetable", bidimensionally-measurable, intracranial lesion that is radiographically recurrent after previous treatment with SRS +/- surgery (craniotomy or LITT). To classify a lesion as radiographically progressive, the lesion must demonstrate a ≥ 25% increase in size following treatment based on the Neuro-Oncology Criteria of Tumor Response for CNS Tumors. To be "targetable" for this study, the lesion should be coverable through a planned single LITT trajectory and thus have a maximum perpendicular diameter (perpendicular to the laser trajectory) of 3 cm. An intra-operative decision to utilize two trajectories is acceptable and patient may remain on study.
3. Patient must be at least 3 months post initial SRS treatment of the target lesion
4. Target lesion must be amenable to undergo surgical biopsy and LITT treatment as determined by the treating neurosurgeon.
5. Frozen pathology diagnosis must be attainable.
6. Patient must be symptomatically stable for a minimum of 3 days prior to the procedure date on a on a max total daily steroid dose equivalent to 4mg of Dexamethasone.
7. ≥18 years of age
8. KPS ≥70
9. Patient is able and willing to complete study requirements
10. Patients with adequate hematologic parameters (all tests to be performed within \<4 weeks of biopsy):
1. ANC ≥ 1.5 X 109/L
2. Platelet count ≥ 100 x 109/L
11. Blood chemistry laboratory value for serum creatinine \< 1.5 x ULN (test to be performed within \<4 weeks of biopsy)
12. Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)
13. All patients of reproductive potential must agree to use an effective method of contraception during the study
14. Patients must be accessible for follow-up
NCT06394570Phase 1, Phase 2Recruiting
University of Texas Southwestern Medical Center · UT Southwestern Medical Center, Dallas, Texas
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for muscle invasive bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Eligibility: 18 Years to · All · 1. Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
2. Ineligibility for cisplatin-based chemotherapy based on treating physician assessment and any of the following "Galsky criteria": renal insufficiency (Creatinine Clearance \<60ml/min by standard institutional calculation method), \>=grade 2 peripheral neuropathy, \>=grade 2 hearing loss, New York Heart Association (NYHA) class III heart failure; a combination of these; or patient refusal.
3. Age \>=18.
4. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
5. Adequate organ and marrow function as defined below:
•Hematologic:
-Absolute neutrophil count (ANC) \>=1500/mm3
* Platelet count \>=100x109/L
* Hemoglobin ≥ 9 g/dL
•Hepatic:
* Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
•Renal:
* No end stage renal disease requiring dialysis allowed
6. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
7.Ability to understand and the willingness to sign a written informed consent.
NCT04083495Phase 2Recruiting
UNC Lineberger Comprehensive Cancer Center · Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill, North Carolina
This is a research study to determine the safety and tolerability of ATLCAR.CD30 for treating relapsed/refractory Peripheral T Cell Lymphoma. Blood samples will be collected from study participants and the immune T cells will be separated. T cells will be genetically modified in a laboratory at UNC-Chapel Hill to enable them to produce CD30 antibody. The modified T cells, called ATLCAR.CD30, will be able to target and attach to lymphoma cancer cells that carry the CD30 antigen. Once they are attached, the hope is that the T cells will attack and destroy the lymphoma cancer cells. To prepare the body for the ATLCAR.CD30 cells, participants will complete lymphodepletion with two chemotherapy agents. Lymphodepletion will happen over three days prior to ATLCAR.CD30 infusion. If participants respond to this treatment, and there are sufficient unused ATLCAR.CD 30 cells, they may be eligible to receive a second infusion. The second infusion will be given after a second lymphodepletion chemotherapy. Most of the clinic visits in this research will last between 1-8 hours.
There are risks associated in participating in this research study. Risks of treatment include infection, fever, nausea, vomiting, neurotoxicity, and cytokine release syndrome which can include low blood pressure or difficulty breathing. Other risks are associated with study procedures, such as biopsies, imaging, infusion, and breach of confidentiality.
Eligibility: 18 Years to 99 Years · All · Inclusion Criteria for the Study
1. Written informed consent and HIPAA authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.
2. Age ≥ 18 years at the time of consent.
3. Karnofsky score of \>60%
4. Histological or cytological evidence/confirmation of CD30+ peripheral T-cell lymphoma per the 2017 World Health Organization Classification of Haematopoietic and Lymphoid Tissues.
5. CD30+ disease determined via archival tissue after the subject's most recent anti-CD30 therapy prior to ATLCAR.CD30 (result can be pending at the time of cell procurement but must be confirmed prior to treatment with the first infusion of ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
6. Any subjects who has received at least two prior lines of therapy for their lymphoma. If transplant is given as a preplanned consolidation in first remission, it will not be counted as a second line of therapy.
7. Any subject who has received one line of therapy who has primary refractory lymphoma or lymphoma that relapsed within 12 months of completing chemotherapy or receiving transplant as long as prior therapy included brentuximab vedotin unless they were not candidates for brentuximab vedotin.
8. Subjects relapsed after autologous stem cell transplant are eligible for this study.
9. Subjects relapsed after allogeneic stem cell transplantation are eligible provided the patient is ≥180 days from transplant, not on immunosuppresive therapy to treat/prevent graft-versus-host disease and has no evidence of active graft-versus-host disease.
10. Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
11. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
12. Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets \<1% failure rate for protection from pregnancy in the product label. Women of childbearing potential will also be instructed to tell their male partners to use a condom.
13. Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Exclusion Criteria for the Study
1. Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study ).
2. Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving \<10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.
3. Active infection with HIV, HTLV, HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for HCV antibody or HCV viral load.
4. Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infecti
NCT05849857Phase 2Recruiting
Oslo University Hospital · Helsinki University Hospital, Helsinki
In this clinical trial adult patients diagnosed with follicular lymphoma and relapse or progression of disease within 24 months of starting first line treatment will be treated with mosunetuzumab. This is a bispecific antibody, a new type of immunotherapy that redirects the bodies own immune cells (T-cells) to attack and kill the lymphoma cells. The main question the trial aims to answer is if mosunetuzumab works better than standard treatments in this sub-group of patients. Patients will receive mosunetuzumab as injections in the abdominal subcutaneous fat once a week for the three first doses, then every third week 7 times. If all signs of disease are gone as evaluated by PET-CT images, the treatment is stopped. If signs of disease remain on PET-CT images, the patients can receive treatment every third week for up to a total of one year. After the end of treatment, patients are followed two years in the trial for signs of progression or relapse.
Eligibility: 18 Years to · All · 1. Written informed consent according to ICH-GCP guidelines.
2. Age ≥ 18 years.
3. Follicular lymphoma grade 1-3a with a current relapse or progression within 24 months of starting 1st line treatment or refractory to 1st line treatment (POD24), more specifically:
1. Documented current relapse or progression of FL within 24 months of starting first line treatment containing a monospecific anti-CD20 antibody (such as rituximab or obinutuzumab with or without chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide).
2. Current lack of response/refractoriness to first line treatment, i.e., no objective response or documented progression within 6 months following at least four cycles of monotherapy with a monospecific anti-CD20 antibody (such as rituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cycles of a monospecific anti CD20 antibody combined with chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide.
3. Received one prior treatment line of systemic therapy.
4. Patients may have had a period of watch and wait before the initiation of first line treatment.
5. Patients may have received localized radiotherapy previously.
4. At least one two-dimensionally measurable lesion with a longest diameter \>15mm.
5. WHO performance status 0-2. Patients with reduced WHO performance status (\> 2) can be considered if reduction in performance is caused by the lymphoma as determined by the investigator.
NCT03340129Phase 2Recruiting
Melanoma Institute Australia · Westmead Hospital, Sydney, New South Wales
This is a phase II, open label, randomised trial of ipilimumab and nivolumab with concurrent intracranial stereotactic radiotherapy versus ipilimumab and nivolumab alone in patients with asymptomatic, untreated melanoma brain metastases.
Eligibility: 18 Years to 120 Years · All · Inclusion Criteria:
1. Female or male patients, ≥18 years of age.
2. Signed, written, informed consent.
3. AJCC Stage IV \[any T, any N, M1d (0) or M1D(1)\] histologically confirmed cutaneous, acral or mucosal unresectable melanoma or unknown primary melanoma and at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm, measurable per RECIST version 1.1 guidelines (modified for brain metastases, enabling up to 5 target lesions in the brain as well as up to 5 extracranial target lesions). There is no upper limit restriction in the number of brain metastases, provided the remaining eligibility criteria are met.
4. The BRAF mutation status must be available prior to randomisation.
5. The treating clinician(s) should consider the intracranial disease amenable to stereotactic radiotherapy over whole brain radiotherapy. Patients for whom there is a definite and immediate indication for radiotherapy (e.g. rapidly progressing disease with associated clinical signs and /or symptoms) should not be considered for enrolment.
6. Brain metastases must be untreated with any modality of radiotherapy or systemic treatment. Previous surgery for melanoma brain metastases is permitted if it resulted in gross total resection and no radiotherapeutic cavity boost was required.
7. No prior systemic treatment for brain metastases is permitted unless given in the neoadjuvant or adjuvant settings for systemic drug the treatment for extracranial disease only. At the time of neoadjuvant or adjuvant systemic therapy for extracranial disease, there should be radiological evidence of the absence of brain metastases. The presenting diagnosis of brain metastases at the time of enrolment in this study must have occurred a minimum of 6 months after stopping neoadjuvant or adjuvant systemic therapy (prior anti PD1, anti PD-L1, anti CTLA-4, BRAF / MEK inhibitors or clinical trial agents) are acceptable in the setting of neoadjuvant or adjuvant treatment
8. Asymptomatic from brain metastases at the time of study enrolment without corticosteroids, analgesia or any other treatment for the management of neurological symptoms (with the exception of antiepileptics prescribed for any reason, provided patient is asymptomatic). Resolved neurological symptoms are permitted if complete resolution, without any intervention, has been sustained for a minimum of 7 days prior to randomisation.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
10. A life expectancy \> 30 days.
11. Able to undergo MRI with Gadolinium contrast agent. CT of the brain is not an acceptable alternative should patients be unable to safely undergo a contrast MRI.
12. Adequate haematological, hepatic and renal organ function as defined by:
1. White cell count ≥ 2.0 × 10x9/L
2. Neutrophil count ≥ 1.5 × 10x9/L
3. Haemoglobin ≥ 90 g/L
4. Platelet count ≥ 100 x 10x9/L
5. Total bilirubin ≤ 1.5 x ULN
6. Alanine transaminase ≤ 3.0 x ULN
7. Aspartate aminotransferase ≤ 3.0 x ULN
8. Serum creatinine ≤ 1.5 x the upper limit of normal (ULN). If serum creatinine is \> 1.5 x ULN, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be 40ml/min to be eligible.
13. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 23 weeks \* after the last dose of study treatment. Effective contraception includes:
1. Intrauterine device with a documented failure rate of less than 1% per year.
2. Vasectomised partner who is sterile prior to the female partner patient's commencement of study treatment and is the sole sexual partner for that female.
3. Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associa
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
NCT06501053NARecruiting
Alexander Valdman · Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer, Stockholm, Solna
The aim of the CORRECT phase 2 study is to show non-inferiority of Contact x-ray brachytherapy (CXB) + short-course radiotherapy (SCRT) compared to the experimental arm of the OPERA trial in organ preservation for early and early intermediate rectal cancer (cT1-3abN1).
Eligibility: 18 Years to · All · * Adenocarcinoma of the rectum classified as:
* cT1-cT3ab, \< 5 cm largest diameter and \< ½ circumference (MRI staging), N0-N1 (\<= 3 nodes \< 8mm diameter), M0
* Performance status (ECOG) 0-1
* Operable patient
* Tumor accessible to endocavitary contact X-ray brachytherapy with a distance from the lower tumor border to the anal verge ≤10 cm
* 18 years or above
* No comorbidity preventing treatment
* Patient having read the information note and having signed the informed consent
* Follow-up possible
NCT06492421Phase 2Recruiting
Second Affiliated Hospital of Guangzhou Medical University · The Second Affiliated Hospital of Guangzhou Medical University, Guanzhou, Guangdong
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.
Eligibility: 18 Years to 75 Years · All · 1. Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
2. Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
3. All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
4. The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
5. Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
6. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
7. Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Hemoglobin \>= 8.0 g/dL; Platelets \>= 100 x 10\^9/L; Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL); Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min.
