A Phase I/II Study Exploring the Safety and Activity of Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients
Overview
- Phase
- Phase 1
- Intervention
- Capecitabine
- Conditions
- Colorectal Cancer Metastatic
- Sponsor
- Gruppo Oncologico del Nord-Ovest
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- recommended dose
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The aim oh this study is to determine the safety and recommended dose of trifluridine/tipiracil plus capecitabine and bevacizumab combination (part 1, dose escalation phase) and to assess its activity in previously untreated mCRC patients who are deemed not eligible for intensive chemotherapy (part 2, expansion phase).
Detailed Description
This is an open-label, multicenter, phase 1/2 study evaluating the safety and activity of trifluridine/tipiracil in combination with capecitabine and bevacizumab in mCRC. The first part (Part 1) of the study will consist in a dose-escalation assessment of the safety of the treatment in subjects with previously untreated mCRC deemed not fit for irinotecan- and/or oxaliplatin- based regimens (i. e. FOLFOX/XELOX/FOLFIRI/FOLFOXIRI with or without targeted agents). The second part (Part 2) will be an open-label phase 2 study with a Fleming's single-stage design to evaluate the ORR of the study treatment at the recommended dose established in the first part of the study in the same patients' population. Trifluridine/tipiracil, capecitabine and bevacizumab will be administered in 28-days cycles until progressive disease, unacceptable toxicities, or patients' refusal.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent to study procedures.
- •Histologically proven diagnosis of colorectal cancer.
- •Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- •At least one measurable lesion according to RECIST1.
- •Age ≥ 18 years.
- •ECOG PS ≤
- •Life expectancy of at least 12 weeks.
- •Previous adjuvant fluoropyrimidine-based chemotherapy allowed only if more than 12 months elapsed between the end of adjuvant and first relapse.
- •Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis.
- •Availability of blood sample for biomarker analysis.
Exclusion Criteria
- •Radiotherapy to any site within 4 weeks before the study.
- •Previous treatment with trifluridine/tipiracil, bevacizumab and capecitabine (previous treatment with capecitabine was permitted only in the adjuvant setting and if more than 12 months elapsed between the end of adjuvant and first relapse).
- •Untreated brain metastases or spinal cord compression or primary brain tumors.
- •History or evidence upon physical examination of CNS disease unless adequately treated.
- •Clinical signs of malnutrition.
- •Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
- •Evidence of bleeding diathesis or coagulopathy.
- •Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
- •Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
- •Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
Arms & Interventions
trifluridine/tipiracil plus capecitabine and bevacizumab
Intervention: Capecitabine
trifluridine/tipiracil plus capecitabine and bevacizumab
Intervention: Bevacizumab
trifluridine/tipiracil plus capecitabine and bevacizumab
Intervention: Trifluridine/Tipiracil
Outcomes
Primary Outcomes
recommended dose
Time Frame: 2 years
recommended dose of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab
activity
Time Frame: 3 years
activity of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of overaal response rate per RECIST v1.1.
Secondary Outcomes
- quality of life for cancer patients(3 years)
- quality of life for colorectal cancer patients(3 years)
- survival(3 years)
- quality of life for dimensions health(3 years)