Ignite Creation Date:
2025-12-25 @ 12:53 AM
Ignite Modification Date:
2025-12-25 @ 11:08 PM
Study NCT ID:
NCT07297667
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-22
First Post:
2025-12-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
GCAR1, a Chimeric Antigen Receptor (CAR) T-CELL Therapy for Relapsed/Refractory GPNMB-Expressing Solid Tumours
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018234', 'term': 'Sarcoma, Alveolar Soft Part'}, {'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}, {'id': 'D064726', 'term': 'Triple Negative Breast Neoplasms'}], 'ancestors': [{'id': 'D009379', 'term': 'Neoplasms, Muscle Tissue'}, {'id': 'D018204', 'term': 'Neoplasms, Connective and Soft Tissue'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D012509', 'term': 'Sarcoma'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C024352', 'term': 'fludarabine'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}], 'ancestors': [{'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-01-31', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2029-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-09', 'studyFirstSubmitDate': '2025-12-09', 'studyFirstSubmitQcDate': '2025-12-09', 'lastUpdatePostDateStruct': {'date': '2025-12-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-12-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To determine the recommended phase II dose (RP2D) of GPNMB directed CAR T cell therapy (GCAR1) in participants with selected tumours (alveolar soft part sarcoma, renal cell carcinoma (excluding clear cell), triple negative breast cancer) expressing GPNMB', 'timeFrame': '3 years'}], 'secondaryOutcomes': [{'measure': 'Number and severity of adverse eventsGCAR1 utilizing CTCAE v5.0', 'timeFrame': '3 years'}, {'measure': 'Overall response rate utilizing RECIST 1.1', 'timeFrame': '3 years'}, {'measure': 'Duration of response', 'timeFrame': '3 years'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Alveolar Soft Part Sarcoma', 'Renal Cell Carcinoma', 'Triple Negative Breast Cancer']}, 'descriptionModule': {'briefSummary': 'This study is being done to answer the following questions:\n\n* Is the new cell therapy, GCAR1, safe to use, and what effects does it have on cancer?\n* What is the right dose of the treatment which could be used in future studies?', 'detailedDescription': "GCAR1 is an autologous chimeric antigen receptor (CAR-T) cell therapy. Autologous means that it is made from a specific person's own white blood cells. These white blood cells are collected from the person and are modified in a laboratory to be able to better find and destroy cancer cells.\n\nWe are doing this study because to find out if this approach is better or worse than the usual approach for cancer. The usual approach is defined as care most people get for this type of cancer.\n\nThe usual approach for patients who are not in a study is treatment with chemotherapy or other anti-cancer drugs. The drugs chosen will depend on the type of cancer. If there is kidney or breast cancer, radiation therapy may also be used. The study doctor can explain which treatment may be best. These treatments can reduce symptoms and may stop the tumour from growing for a few months or longer."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '15 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Archival tumour specimen must be positive for GPNMB expression by central laboratory testing, defined as ≥ 50% of tumour cells with 2+ or 3+ staining intensity by immunohistochemistry.\n* Participants must have a histologically and/or cytologically confirmed diagnosis of one of the following tumours that is advanced/ metastatic/ recurrent or unresectable, for which no curative therapy exists.\n\n * alveolar soft part sarcoma\n * renal cell carcinoma (excluding clear cell)\n * triple negative breast cancer (ER, PR and HER-2 negative as defined by ASCO/CAP criteria)\n* Participants must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block.\n* Presence of radiologically documented disease. All radiology studies must be performed within 28 days of enrollment and repeated 14 days prior to lymphodepletion. All participants must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows:\n\n * Chest x-ray ≥ 20 mm\n * CT scan (with slice thickness of 5 mm) 10 mm -\\> longest diameter\n * Physical exam (using calipers) ≥ 10 mm\n * Lymph nodes by CT scan ≥ 15 mm -\\> measured in short axis\n* ASPS participants must be ≥ 15 years of age.\n* TNBC and RCC participants must be ≥ 18 years of age.\n* ECOG performance status of 0 or 1 or Karnofsky or Lansky \\> 60.\n* Anticipated life expectancy of ≥ 6 months.\n* Participants must have received prior systemic therapy as shown below; exceptions may be made if further systemic (bridging) therapy needs to be given following leukapheresis but must be agreed by CCTG. For heavily pre-treated participants (i.e. those that have received greater than 3 lines of treatment), please contact CCTG prior to screening/ enrollment to discuss.\n\n * ASPS - completed all systemic therapy available that has been shown to improve survival (unless contraindicated).\n * TNBC\n\n 1. Progressive disease following at least one line of systemic treatment for metastatic disease which must include an ADC (all participants) and an ICI (participants whose tumours express PD-L1). Contact CCTG if participants are not eligible for ADC/PD-L1 therapy.\n 2. No more than 3 lines of treatment for metastatic disease.\n 3. Must have had at least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, which must have included an anthracycline and a taxane (unless contraindicated). Select participants that have not received both anthracycline and taxane therapy may be considered eligible after discussion with CCTG.\n * RCC - must have progressive disease following at least one line of systemic treatment for metastatic disease that must have included an ICI and a VEGFR targeted agent (unless contraindicated).\n* Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior therapies. Adequate washout as follows prior to both keukapheresis and lymphodepletion must have occurred. Longest of one of the following:\n\n * 3 weeks for cytotoxic chemotherapy or 4 weeks for immunotherapy\n * 5 half lives for investigational agents (only applicable prior to leukapheresis; not permitted between leukapheresis and lymphodepletion)\n * Standard cycle length of standard therapies\n* Previous major surgery is permitted provided that surgery occurred at least 21 days prior to participant enrollment and that wound healing has occurred.\n* Prior external beam radiation is permitted provided a minimum of 28 days have elapsed between the last dose of radiation and date of enrollment. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiotherapy is not permitted.\n* Absolute neutrophils ≥ 1.5 x 10\\^9/L; Platelets ≥100 x 10\\^9/L; Hemoglobin ≥80g/L; Absolute lymphocyte count ≥150/uL; Coagulation (INR/PT and PTT) within normal limits; Bilirubin ≤ ULN; AST ≤2.5 x UNL; ALT ≤5.0 x UNL if participant has liver metastases; Creatine clearance ≥40mL/min\n* Consent and assent, when applicable, must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant or their parent/ legal guardian (if applicable) must sign a consent form prior to screening onto the trial to document their willingness to participate.\n* Fit for leukapheresis and has adequate venous access for cell collection.\n* Participants must be accessible for treatment and follow up. Participants enrolled on this trial must be treated and followed at the participating centre for a minimum of 12 months or for as long as is deemed necessary by the treating physician and after discussion with CCTG.\n* Participants must agree to return to their enrolling site for any adverse events which may occur within the first 12 months of treatment or as long as deemed necessary by their trial physician and be, in the opinion of the investigator, able to comply with all protocol-required study visits or procedures, including follow-up visits or comply with study requirements for participation.\n* In accordance with CCTG policy, leukapheresis must be performed within 5 working days of participant enrollment.\n* Participants of childbearing potential must have agreed to use a highly effective contraceptive method.\n\nExclusion Criteria:\n\n* Participants 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. However, participants on active anticancer therapy for other advanced or metastatic malignancies are not eligible. Consult CCTG for participants who are on adjuvant therapies after curative surgery or in instances where it is felt the participant may be eligible (for example, TCC bladder receiving local therapies or CLL not requiring active therapy).\n* Concurrent treatment with other anti-cancer therapy (see Section 4.1.8, if there is a considerable delay between enrollment and lymphodepletion/GCAR1 infusion, bridging treatments can be considered after discussion with CCTG).\n* Prior therapy with\n\n * a gene therapy product or any adoptive T cell therapy\n * prior GPNMB targeting therapy.\n* Live attenuated vaccination administered within 30 days prior to or planned within 30 days after GCAR1 therapy.\n* Participants who require continued or concurrent systemic steroid therapy (at doses more than 10 mg / day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to GCAR1 treatment. Topical applications, inhaled sprays, eye drops or local injections (e.g. intra-articular) are permissible.\n* Primary immunodeficiency or history of severe autoimmune disease (including: Crohn's disease, rheumatoid arthritis, systemic lupus) requiring immunosuppressive agents/ systemic disease modifying agents within 2 years of enrollment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n* Participants with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the participant to be managed according to the protocol including but not limited to:\n\n * Hepatitis B or C virus (HBV or HCV). For participants with previous HBV or HCV infection who are currently on treatment, they are eligible if they have an undetectable viral load via quantitative PCR and/or nucleic acid testing\n * HIV positive by serology and PCR\n * Uncontrolled fungal, bacterial, viral or other infection\n * Current infection with HTLV-1\n * Tuberculosis\n * Syphilis\n * West Nile Virus\n* Participants who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or who have had unstable angina congestive heart failure or myocardial infarction within the previous year. All participants should have a LVEF ≥45% as evaluated by echocardiogram or MUGA, an electrocardiogram with no clinically significant features including QTc\\<450 msec\\* and oxygen saturations on room air ≥92%.\n* Known sensitivity or allergy to fludarabine, cyclophosphamide or any of their components, or to GCAR1 or any of its components, including DMSO and HSA.\n* Active intracerebral metastases or leptomeningeal disease. Participants who have received definitive treatment, are clinically stable and do not require corticosteroids are eligible to participate in the trial. Participants with treated and stable intracerebral metastases will need to undergo imaging surveillance (See Section 5.0).\n* Pregnant or breastfeeding women."}, 'identificationModule': {'nctId': 'NCT07297667', 'briefTitle': 'GCAR1, a Chimeric Antigen Receptor (CAR) T-CELL Therapy for Relapsed/Refractory GPNMB-Expressing Solid Tumours', 'organization': {'class': 'NETWORK', 'fullName': 'Canadian Cancer Trials Group'}, 'officialTitle': 'A Phase I Study of GCAR1, a Chimeric Antigen Receptor (CAR) T-CELL Therapy for Participants With Selected Relapsed/Refractory GPNMB-Expressing Solid Tumours', 'orgStudyIdInfo': {'id': 'I246'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'GCAR1 Infusion', 'interventionNames': ['Drug: Fludarabine', 'Drug: Cyclophosphamide', 'Biological: GCAR1']}], 'interventions': [{'name': 'Fludarabine', 'type': 'DRUG', 'description': '40mg/m2 IV', 'armGroupLabels': ['GCAR1 Infusion']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': '600mg/m2 IV', 'armGroupLabels': ['GCAR1 Infusion']}, {'name': 'GCAR1', 'type': 'BIOLOGICAL', 'description': 'Assigned at enrollment', 'armGroupLabels': ['GCAR1 Infusion']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Laura Pearce', 'role': 'CONTACT', 'email': 'lpearce@ctg.queensu.ca', 'phone': '613-533-6430'}, {'name': 'Mariam Jafri', 'role': 'CONTACT', 'email': 'mjafri@ctg.queensu.ca', 'phone': '613-533-6430'}], 'overallOfficials': [{'name': 'Mona Shafey', 'role': 'STUDY_CHAIR', 'affiliation': 'Tom Baker Cancer Centre, Calgary, Alberta, Canada'}]}, 'ipdSharingStatementModule': {'url': 'https://www.ctg.queensu.ca/public/policies', 'ipdSharing': 'YES', 'description': 'According to CCTG Policies'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Canadian Cancer Trials Group', 'class': 'NETWORK'}, 'responsibleParty': {'type': 'SPONSOR'}}}}