A Phase I/II Study of IXO With Bevacizumab in Patients With Metastatic Colorectal Cancer

Phase 2TerminatedNCT00819754

Ottawa Hospital Research Institute23 enrolled

Overview

Triplets of irinotecan, oxaliplatin and infusional 5-fluorouracil(FU)/leucovorin (LV) are associated with high response rates and long survival as first-line treatment for metastatic colorectal cancer (mCRC). The oral fluoropyrimidine, capecitabine, is better tolerated and shows better response rates than 5-FU/LV in metastatic colorectal cancer. A phase I dose-escalation study established dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of irinotecan, oxaliplatin and capecitabine. This phase I /II study is to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), phase II recommended dose (RD) of IXO and bevacizumab combination and safety at the RD in an expanded cohort.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Colorectal Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically documented adenocarcinoma of the colon or rectum. * Advanced and/or metastatic disease, incurable with standard therapy. * Unresectable advanced and/or metastatic unidimensionally measurable disease (RECIST scale). * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 * Age: over 18 years. * Adequate haematological, renal and hepatic functions * Patient consent must be obtained according to local REB requirements. * Patients must be accessible for treatment and follow up. Exclusion Criteria: * Previous or concurrent malignancies * Pregnant or lactating women. Women of childbearing potential must have had a negative pregnancy test within 7 days prior to registration. * Concurrent treatment with other experimental drugs or anticancer therapy. * Previous chemotherapy for advanced and/or metastatic disease. * Previous adjuvant therapy with irinotecan or oxaliplatin. * Previous full dose curative pelvic radiation therapy. * Patients with documented brain metastases. * Serious illness or medical condition. * Gilbert's disease * Use of enzyme inducing anticonvulsants such as phenytoin, phenobarbital and carbamazepine

Outcomes

Primary Outcomes

Phase I: Assess the MTD and RD for phase II of IXO and bevacizumab combination given every 3 weeks in 1st line patients with mCRC

Time frame: 3-week cycle, continuous monitoring of AE

Phase II: Using the RD established in phase I, assess efficacy of the IXO with bevacizumab combination as measured by progression-free survival

Time frame: 3-week cycle, continuous monitoring of AE

Secondary Outcomes

Response rates and duration of response

Time frame: every 2 cycles - 6 weeks

Overall survival

Time frame: continuous

Qualitative and quantitative toxicity