TEMOZOLOMIDE for Metastatic colorectal cancer | Colorectal cancer

Inclusion criteria

• {"criterion_text":"- 1. Signed written informed consent according to ethics committee requirements\n- 2.\tAge ≥18 years\n- 3.\tMetastatic or non-resectable adenocarcinoma of the colon or rectum\n- 4.\tMSS or pMMR confirmed locally by PCR or IHC, respectively\n- 5.\tMGMT promoter methylation confirmed by PCR and IHC in solid tumor tissue\n- 6.\tPrior therapy with oxaliplatin, irinotecan and fluoropyrimidin based chemotherapy (or intolerance to these). Prior cetuximab, panitumumab, bevacizumab, aflibercept, regorafenib or trifluridine/tipiracil is allowed but not mandatory.\n- 7.\tECOG performance status 0-1\n- 8.\tWoman of childbearing potential must have been tested negative in a serum pregnancy test within 5 days prior to randomization. Fertile patients must agree to use a highly effective method of birth control (see appendix 2 – highly effective methods of contraception) during the study and for six months after the discontinuation of study medication.\n- 9.\tAdequate bone marrow function and organ function: a. Absolute neutrophil count (ANC) > 1.5 x 109/l and platelets (pl) > 100 x 109/l b. Serum bilirubin < 1.5 × upper limit of normal (ULN); and AST/ALT < 2.5 × ULN (or < 5 × ULN in patients with liver metastases). c. Estimated (eGFR) or measured glomerular filtration rate (GFR) > 50 ml/min"}

Exclusion criteria

• {"criterion_text":"- 1.\tAny condition requiring a daily dose of more than 10 mg prednisolone (or any other corticosteroid of equivalent strength), or any other immunosupressant, e.g. but not limited to mycophenolate and anti-TNF agents.\n- 10.\tClinically significant cardiovascular disease, such as recent cerebrovascular accidents or myocardial infarction within 6 months of study enrollment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or higher congestive heart failure, or severe uncontrolled cardiac arrhythmia.\n- 11.\tSymptomatic brain metastases, or radiographic evidence of progression of known brain metastases within 8 weeks of entry in the study.\n- 12.\tPregnancy or breastfeeding\n- 13.\tAny other condition or therapy, which in the investigators opinion may pose a risk to the patient or interfere with the study objectives.\n- 2.\tHistory of autoimmune disease. Exceptions are adequately controlled autoimmune induced hypothyroidism, type 1 diabetes. Psoriasis or vitiligo are allowed as long as no systemic treatment is required.\n- 3.\tSignificant co-morbidity that the investigator considers inadequately controlled, or that would make the patient unable to tolerate study treatment.\n- 4.\tPatients with known hypersensitivity to any of the study drugs or their excipients.\n- 5.\tInability to swallow tablets.\n- 6.\tMalabsorption, significant bowel resection, or any other disease that would significantly inhibit bowel absorption.\n- 7.\tPrevious treatment with temozolomide.\n- 8.\tConcurrent secondary active malignancy.\n- 9.\tPatients with either homozygosity or compound heterozygosity for multiple gene variants of dihydropyrimidine dehydrogenase (DPD), leading to a significant reduction in 5-FU metabolism do not meet eligibility criteria. However, those with decreased DPD activity who have previously tolerated 5-FU treatment can participate with capecitabine dosed according to the latest tolerated dose of capecitabine or 5FU."}

Primary endpoints

• {"endpoint_text":"- Disease control rate (DCR) (complete response (CR), PR, or SD) evaluated by a CT scan 16 weeks after initiation of TemCap.","definition_or_measurement_approach":"Evaluated by a CT scan 16 weeks after initiation of TemCap; DCR includes complete response (CR), partial response (PR), or stable disease (SD)."}

Secondary endpoints

• {"endpoint_text":"- 1. PFS for patients initiating TemCap and for patients initiating TemCap with ipi-nivo","definition_or_measurement_approach":"Progression-free survival (PFS) (method/timing not further specified in JSON)."}
• {"endpoint_text":"- 2. OS for patients initiating TemCap and for patients initiating TemCap with ipi-nivo","definition_or_measurement_approach":"Overall survival (OS) (method/timing not further specified in JSON)."}
• {"endpoint_text":"- 3. ORR according to RECIST 1.1 criteria","definition_or_measurement_approach":"Objective response rate (ORR) assessed according to RECIST 1.1 criteria."}
• {"endpoint_text":"- 4. Safety and tolerability of the combination of ipi-nivo and TemCap","definition_or_measurement_approach":"Safety and tolerability assessed by adverse event reporting and related safety assessments (detailed methods not specified in JSON)."}
• {"endpoint_text":"- 5. Quality of life measured by the EORCT QLQ-C30 questionnaire","definition_or_measurement_approach":"Quality of life measured using the EORTC QLQ-C30 questionnaire."}

Denmark

Earliest CTIS Part Ii Submission Date

11-09-2025

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

13

Number Of Sites

3

Number Of Participants

165

Primary sponsor

Full Name

Odense University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"codes: 1,10,7,8","organisation_type":"Hospital/Clinic/Other health care facility"}