Prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of active post-resection/ablation therapy in patients with metastatic colorectal cancer
- Conditions
- colorectal cancerC18Malignant neoplasm of colon
- Registration Number
- DRKS00027138
- Lead Sponsor
- Charité Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 507
1. Patient's signed informed consent.
2. Patient's age =18 years at the time of signing the informed consent.
3. Histologically confirmed adenocarcinoma of the colon or rectum.
4. Resected (R0 or R1) and/or effectively treated metastases (all techniques allowed) of colorectal cancer within 3-10 weeks before randomization (earlier randomisation allowed if at least 3 weeks interval between intervention and treatment start is guaranteed) AND resected primary tumor (synchronous or metachronous). In cases of synchronous metastases the interval of 3-10 weeks might be calculated following the removal of the primary tumor if this intervention was the last to address all tumor lesions.
5. Absence of significant active wound healing complications (if applicable) at randomization. Resolved wound healing complications after resection/ablation are acceptable for inclusion into the trial.
6. 6.No radiographic evidence of active metastatic disease at study entry in a CT and/or MRI scan not older than 10 weeks prior randomization. Pre-surgery/ablation images are eligible for the study if all lesions have been addressed in the interval.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Adequate bone marrow, hepatic and renal organ function, defined by the following laboratory test results:
Absolute neutrophil count = 1.5E+9/L (1500/µL)
Hemoglobin = 80 g/L (8 g/dL)
Platelet count = 100E+9/L (100000/µL) without transfusion
Total serum bilirubin of = 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST/GOT) = 3.0 × ULN.
Calculated glomerular filtration rate (GFR) according to Cockcroft-Gault formula or according to MDRD = 50 mL/min or serum creatinine = 1.5 x ULN
9. Patients without anticoagulation need to present with an international normalized ratio (INR) < 1.5 x ULN and prothrombin time (PTT) < 1.5 x ULN. Patient with prophylactic or therapeutic anticoagulation are allowed into the trial.
10. Proficient fluorouracil metabolism as defined:
10.1 Prior treatment with 5-FU or capecitabine without unusual toxicity or
10.2 If tested, normal dihydropyrimidine dehydrogenase (DPD) deficiency test according to the standard of the study site or
10.3 If tested, in patients with DPD deficiency test with a Clinical Pharmacogenetics Implementation Consortium (CPIC) activity score of 1.0-1.5 fluoropyrimidine dosage should be reduced by 50%
11. For women of childbearing potential (WOCBP): negative pregnancy test within 14 days before randomization and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study treatment.
A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male partner's sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
For men: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during th
1. Treatment of metastases greater than 3 cm with radio-frequency/microwave ablation within 24 months prior to study entry if applicable.
2. Treatment of metastases greater than 5 cm with radiation (stereotactic/ brachytherapy) within 24 months prior to study entry if applicable.
3. Previous chemotherapy at any time for metastatic or localized disease with > 6 cycles of FOLFOX (or FOLFOXIRI) or > 4 cycles of CAPOX/XELOX. Any other pretreatment is permitted, including unlimited use of antibodies, fluoropyrimidines and irinotecan.
4. New York Heart Association Class III or greater heart failure by clinical judgement.
5. Myocardial infarction within 6 months prior to randomization; percutaneous transluminal coronary angioplasty (PTCA) with or without stenting within 6 months prior to randomization.
6. Unstable angina pectoris.
7. Unstable cardiac arrhythmia > grade 2 NCI CTCAE despite anti-arrhythmic therapy.
8. Ongoing toxicities > grade 2 NCI CTCAEn particular peripheral neuropathy.
9. Active uncontrolled infection by investigator's perspective.
10. Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
11. Known hypersensitivity to 5-FU, leucovorin, irinotecan or oxaliplatin or to any of the other excipients listed in section 6.1 of the corresponding Summary of Product Characteristics (SmPC).
12. Recent or concomitant treatment with brivudine.
13. Peripheral sensitive neuropathy with functional impairment (> grade 1 acc. to CTCAE version 5.0 (see appendix)).
14. Inflammatory bowel disease and/or bowel obstruction.
15. Simultaneous application of Johannis herbs preparations.
16. Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.
17.Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to randomization or at least to intended treatment start or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure.
18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
19. Medical history of malignant disease other than metastatic colorectal cancer (mCRC) with the following exceptions:
19.1 patients who have been disease-free for at least three years before randomization
19.2 patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine cancer
19.3 patients with any treated or untreated malignant disease that is associated with a 5-year survival prognosis of = 90% and does not require active therapy
20. Known alcohol or drug abuse.
21. Pregnant or breastfeeding females.
22. Participation in a clinical trial or experimental drug treatment within 28 days prior to potential inclusion in the clinical trial or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment prior to potential inclusion in the clinical trial, depending on which period is longest, or simultaneous participation in another clinical trial while taking part in this clinical trial.
23. Patients depended on Sponsor, investigator or study site.
24. Suspected SARS-CoV-2 infection with or without symptoms (evaluatio
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) defined as time from randomization to death or evidence of disease as defined by RECIST 1.1. criteria (whatever occurs first).
- Secondary Outcome Measures
Name Time Method Overall survival (OS) as time from randomization to the date of death of any cause. <br>Number and type of treatments (including efficacy) beyond study participation.<br>Compare the safety of active treatment with strictly structured follow-up care, based on adverse events.<br>Patient reported quality of life questionnaires.