IRINOTECAN for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- Histological documentation of adenocarcinoma of the colon or rectum"}
• {"criterion_text":"- Patients with metastatic colorectal cancer"}
• {"criterion_text":"- Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti-VEGF therapy and an anti-EGFR therapy (for RAS wild-type tumors), encorafenib"}
• {"criterion_text":"- ECOG performance status ≤1"}
• {"criterion_text":"- Life expectancy of at least 3 months"}
• {"criterion_text":"- Patients with A/A CCND1 genotype of rs603965 CCND1"}
• {"criterion_text":"- International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care"}

Exclusion criteria

• {"criterion_text":"- Patients with A/G or G/G CCND1 genotype of rs603965 CCND1"}
• {"criterion_text":"- Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)"}
• {"criterion_text":"- Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea)"}
• {"criterion_text":"- Ongoing infection > Grade 2 NCI-CTCAE V5.0"}
• {"criterion_text":"- Known history of human immunodeficiency virus (HIV) infection"}
• {"criterion_text":"- Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy"}
• {"criterion_text":"- Patients with seizure disorder requiring medication"}
• {"criterion_text":"- History of organ allograft"}
• {"criterion_text":"- Patients with evidence or history of any bleeding diathesis, irrespective of severity"}
• {"criterion_text":"- Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication"}
• {"criterion_text":"- Non-healing wound, ulcer, or bone fracture"}
• {"criterion_text":"- Prior treatment with regorafenib or sorafenib"}
• {"criterion_text":"- Dehydration NCI-CTCAE V5.0 Grade ≥ 1"}
• {"criterion_text":"- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation"}
• {"criterion_text":"- Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours)"}
• {"criterion_text":"- Patients unable to swallow oral medications"}
• {"criterion_text":"- Any malabsorption condition"}
• {"criterion_text":"- Chronic inflammatory bowel disease and / or bowel obstruction"}
• {"criterion_text":"- Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity ≤ Grade 2"}
• {"criterion_text":"- Concomitant intake of St. John's wort"}
• {"criterion_text":"- History of gastrointestinal fistula or perforation"}
• {"criterion_text":"- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non invasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)]."}
• {"criterion_text":"- Prior treatment with TAS 102"}
• {"criterion_text":"- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug"}
• {"criterion_text":"- Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug"}
• {"criterion_text":"- Congestive heart failure ≥ New York Heart Association (NYHA) class 2"}
• {"criterion_text":"- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)"}
• {"criterion_text":"- Myocardial infarction less than 6 months before start of study drug"}
• {"criterion_text":"- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)"}

Primary endpoints

• {"endpoint_text":"- Overall survival presented with its median and confidence interval at 95%, estimated from randomization date to the date of death, whatever the cause, using the Kaplan-Meier method.","definition_or_measurement_approach":"Estimated from randomization date to date of death from any cause, presented as median and 95% confidence interval, estimated using the Kaplan-Meier method."}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to Deterioration","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease control rate","definition_or_measurement_approach":"Disease control rate assessed according to RECIST criteria (version 1.1) (see secondary objective: 'Disease control rate according to Recist criteria (version 1.1)')"}
• {"endpoint_text":"- Objective response rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety according version 5 of NCI-CTCAE","definition_or_measurement_approach":"Safety/toxicity graded according to NCI-CTCAE version 5.0"}
• {"endpoint_text":"- Quality of life (EORTC QLQ-C30)","definition_or_measurement_approach":"Quality of life measured using the EORTC QLQ-C30 instrument"}

France

Earliest CTIS Part Ii Submission Date

19-06-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

497

Number Of Sites

11

Number Of Participants

78

Primary sponsor

Full Name

Institut Regional Du Cancer De Montpellier

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France