None listed
Conditions
Brief summary
The purpose of this study is to assess the effect of delivering all anti-cancer medications during initial systemic therapy on outcomes in those undergoing treatment for metastatic colorectal cancer. Who is it for? You may be eligible for this study if you are an adult who has been diagnosed with metastatic colorectal cancer. Study details Participants will be randomly allocated to receive one of two treatments: 1. Alternating schedule of 2 cycles of oxaliplatin based chemotherapy and 2 cycles of irinotecan based chemotherapy 2. Clinician’s choice of chemotherapy. Participants will receive combination chemotherapy for 4-6 months followed by a maintenance period where participants will continue to receive 'maintenance' chemotherapy until disease progression, toxicity or patient/treating clinician request. It is hoped that combining the two effective chemotherapy drugs in first line treatment, but in an alternating pattern, will be beneficial to the patient's outcome and that this alternating use of them will reduce the higher toxicity that occurs when these drugs are used together.
Interventions
Alternating oxaliplatin and irinotecan doublet treatment schedules.
Arm A: Clinician’s choice doublet chemotherapy (standard chemotherapy)
Arm B: Alternating schedule of 2 cycles of oxaliplatin doublet chemotherapy and 2 cycles of irinotecan doublet chemotherapy, i.e. mFOLFOX6-FOLFIRI or CAPOX-CAPIRI
In both arms, initial combination chemotherapy will be given for 4-6 months as per standard of care, followed by maintenance fluoropyrimidine chemotherapy until disease progression, unmanageable t
Alternating oxaliplatin and irinotecan doublet treatment schedules. Arm A: Clinician’s choice doublet chemotherapy (standard chemotherapy) Arm B: Alternating schedule of 2 cycles of oxaliplatin doublet chemotherapy and 2 cycles of irinotecan doublet chemotherapy, i.e. mFOLFOX6-FOLFIRI or CAPOX-CAPIRI In both arms, initial combination chemotherapy will be given for 4-6 months as per standard of care, followed by maintenance fluoropyrimidine chemotherapy until disease progression, unmanageable toxicity or patient or treating clinician’s request. Biologic therapy (bevacizumab or an EGFR inhibitor) will be given according to clinician’s choice; however, as per guidelines, EGFRI use will be restricted to patients with left-sided RAS wild-type tumours. 1) Intervention drug - Doublet chemotherapy (mFOLFOX6, FOLFIRI, CAPOIX or CAPIRI) mFOLFOX6 Frequency: every 2 weeks Oxaliplatin 85 mg/m2 IV day 1 Leucovorin 50 mg IV day 1 Fluorouracil (5FU) 400 mg/m2 IV day 1 Fluorouracil (5FU) infusion 2,400 mg/m2 over 46 hours day 1-2 FOLFIRI Frequency: every 2 weeks Irinotecan 180 mg/m2 IV day 1 (150 mg/m2 if > 70 y.o.) Leucovorin 50 mg IV day 1 Fluorouracil (5FU) 400 mg/m2 IV day 1 Fluorouracil (5FU) infusion 2,400 mg/m2 over 46 hours day 1-2 CAPOX Frequency: every 3 weeks Oxaliplatin 130 mg/m2 IV day 1 Capecitabine 850-1000 mg/m2 orally BD days 1-14 CAPIRI Frequency: every 3 weeks Irinotecan 240 mg/m2 IV day 1 Capecitabine 850-1000 mg/m2 orally BD days 1-14 New drug schedules have been created for the hospital staff to keep track of the alternating cycles. Whether a participant receives mFOLFOX6-FOLFIRI or CAPOX-CAPIRI is decided by the treating practitioner, based on their usual treatment practice. When a patient is on the interventional treatment e.g. CAPOX-CAPIRI, the different treatments are staggered every 3 weeks. For FOLFOX-FOLFIRI, the the different treatments are staggered every 2 weeks. 2) This is an open-label, prospective, multi-centre registry-based study evaluating the impact of delivering all active cytotoxic agents during initial systemic therapy on outcomes in treatment-naïve mCRC. Participants will be randomised in a 1:1 ratio to one of two treatment arms and followed according to standard protocols, with treatment, toxicity and outcome data captured in the TRACC registry.
Sponsors
The Walter and Eliza Hall Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria 1. Signed informed consent obtained prior to any study specific procedures and willingness to comply with study requirements 2. Age greater than or equal to 18 years 3. Histologically confirmed, metastatic colorectal adenocarcinoma treated with less than or equal to 2 cycles of doublet chemotherapy 4. ECOG performance status of 0-2 5. Life expectancy of greater than or equal to 3 months 6. Adequate major organ function to receive doublet chemotherapy as judged by the treating clinician 7. No contraindication to any of the 3 cytotoxic agents (5FU, oxaliplatin and irinotecan) 8. Recent imaging of chest, abdomen and pelvis. It is recommended that this should be within 4 weeks of first chemotherapy dose (no more than 8 weeks). Please note: Every patient enrolled in the study is then entered in the TRACC Registry to enable the data collection for the study.
Exclusion criteria
Exclusion Criteria 1. Previous chemotherapy and/or biologic therapy for CRC, except for adjuvant treatment if completed more than 6 months earlier 2. Not suitable for doublet chemotherapy 3. Significant concomitant medical condition which the treating clinician believes precludes the patient from enrolling in the study
Outcome results
None listed