3C-14-5: A Double-blind, Randomized, Placebo Controlled Phase III Study of Nintedanib plus Best Supportive Care (BSC) versus Placebo plus BSC in Patients with Colorectal Cancer Refractory to Standard Therapies
Description
Detailed Description
Colorectal cancer is the second leading cause of cancer-related deaths in Western countries. About half of patients eventually develop metastatic disease. Virtually all patients with advanced metastatic colorectal cancer will sooner or later become refractory to standard treatment, and will eventually succumb to their disease.
Despite clinical advances reported in the treatment of metastatic colorectal cancer by using combination of chemotherapy and targeted therapies, there is need for more effective agents for patients with refractory metastatic colorectal cancer.
VEGFR-2 is considered the crucial molecule involved in formation as well as the maintenance of tumor. Nintedanib is a potent small molecule inhibiting VEGFR receptor family, leading to anti-tumor effects.
The purpose/objective of this study is to evaluate the efficacy and safety of nintedanib in
patients with metastatic colorectal cancer after failure of previous treatment with standard chemotherapy and biological agents.
Study participants will be randomly assigned in a 1:1 ratio to receive either nintedanib + best supportive care (Arm A) or matching placebo + best supportive care (Arm B). Best supportive care that is considered standard treatment option after failure of approved available anti-cancer treatments.
Participants will receive study treatment until unequivocal progression or undue toxicity; no other anti-cancer treatment will be allowed until study drug is discontinued.
Evaluation of tumor response will be assessed by imaging every 6 weeks. The investigators decision about continuation of study treatment will be based on assessment of tumor response and progression.
Phase
Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.Inclusion and Exclusion Criteria
- Age >= 18 years
- Signed informed consent
- Histologically or cytologically confirmed colorectal adenocarcinoma
- Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status = 1
- At least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
- Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
- fluoropyrimidine
- oxaliplatin: Patients treated with oxalipatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease
- irinotecan
- bevacizumab or aflibercept
- cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
- previous treatment with regorafenib is allowed
- Life expectancy of at least 12 weeks
- Hepatic function: aspartate aminotransferase (AST)/ Alanine Amino Tranferase (ALT) = 1.5 X Upper Limit of Normal (ULN) and bilirubin = ULN for patients without liver metastases. AST/ALT = 2.5 X ULN and bilirubin = ULN for patients with liver metastases. Patients with Gilbert syndrome and bilirubin < 2 X ULN and normal AST/ALT are eligible
- Coagulation parameters: International normalised ratio (INR) < 2 and prothrombin Time (PTT) = 2xULN
- Previous treatment with nintedanib
- toxicity attributed to previous anticancer therapy that did not resolve to Common Terminology Criteria for Adverse Events (CTCAE) grade =1
- History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.
- Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
- Significant cardiovascular diseases
- History of severe haemorrhagic or thromboembolic event in the past 12 months
- Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring
- Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug
- Patient with brain metastases that are symptomatic and/or require therapy.
- Patients of childbearing potential who are sexually active and unwilling to use a highly effective method of contraception
- Pregnancy or breast-feeding.
Sites
Please contact Poornima Murali to learn more about where you can participate in this trial. Please use the contact form on the right side.
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