Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic, Cancer, Colorectal, Colorectal Cancer, Colon, Rectum, Metastasis
Brief summary
The main purpose of this study is to demonstrate the superiority of S 95005 in combination with bevacizumab over capecitabine in combination with bevacizumab.
Interventions
Film-coated tablets of S 95005 (35 mg/m²/dose) will be administered orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; This treatment cycle will be repeated every 4 weeks.
DRUGCapecitabine
Film-coated tablets, Capecitabine (1250 mg/m²/dose) will be administered orally BID on Days 1-14 of each cycle. This treatment cycle will be repeated every 3 weeks.
BIOLOGICALBevacizumab experimental
Concentrate for solution for infusion, Bevacizumab (5 mg/kg, IV) administered every 2 weeks (Day 1 and Day 15). This treatment cycle will be repeated every 4 weeks.
BIOLOGICALBevacizumab control
Concentrate for solution for infusion, Bevacizumab (7.5 mg/kg, IV) will be administered on Day 1 of each cycle.This treatment cycle will be repeated every 3 weeks.
Sponsors
ADIR, a Servier Group company
Institut de Recherches Internationales Servier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known. 2. RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not available at the time of randomisation, tumour biopsy must be available for RAS status determination (based on local biological assessment). 3. Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin 4. Patient is not a candidate for curative resection of metastatic lesions. 5. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer. 6. ECOG (Eastern Cooperative Oncology Group) performance status ≤2. 7. Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol'
Exclusion criteria
8. Pregnancy, breastfeeding or possibility of becoming pregnant during the study. 9. Participation in another interventional study within 4 weeks prior to the randomisation . 10. Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation. 11. Symptomatic central nervous system metastases. 12. Major surgery within 4 weeks prior to the randomisation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 24 months | Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to 8 years | The proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and using investigator's tumour assessment. |
| Disease control rate (DCR) | Up to 8 years | The proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST 1.1 criteria and using investigator's tumour assessment. |
| Duration of response (DoR) | Up to 8 years | The time from the first documentation of response (CR or PR) to the first documentation of objective tumour progression or death due to any cause, whichever occurs first. |
| Time to treatment failure (TTF) | Up to 8 years | The time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death. |
| Incidence of Adverse Events (AEs) | Up to 8 years | — |
| Overall Survival (OS) | Up to 8 years | Time elapsed between the date of randomization and the date of death due to any cause. |
| Changes in ECOG performance status | Up to 8 years | — |
| Number of clinically significant changes to blood pressure, heart rate, body temperature and body weight | Up to 8 years | — |
| Number of clinically significant changes to 12-leads ECG parameters | Up to 8 years | — |
| Quality of life as assessed by EORTC QLQ-C30 | Up to 8 years | European organization for research and treatment of cancer (EORTC) Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) scores range from 0-100 and assess functional and symptom scores. For functional scores, a higher score represents an increase in functioning. For symptom scores, a higher score represents an increase in symptoms. |
| Quality of life as assessed by EQ-5D-5L | Up to 8 years | The 5-level EQ-5D version questionnaire scores range from 5 to 25 with a higher score representing a worse health status. |
| Number of clinically significant changes to hematology, biochemistry, coagulation and urinalysis tests | Up to 8 years | — |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Czechia, Denmark, Estonia, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Slovakia, Spain, Sweden, Ukraine, United Kingdom
Outcome results
None listed