A Phase I/II Study of XELOXIRI and Bevacizumab as First-line Treatment in Metastatic Colorectal Cancer

NCT ID: NCT04380103

Last Updated: 2020-05-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-26
• Study Completion Date: 2022-09-30

Brief Summary

The phase I/II study was designed to evaluate if the regimen of Irinotecan, Oxaliplatin, Capecitabine (XELOXIRI) and Bevacizumab is a superior first-line option for patients with metastatic colorectal cancer(mCRC) in terms of safety and efficacy.

Detailed Description

Recent studies have shown that the triplet-drug regimen FOLFOXIRI (irinotecan/oxaliplatin/fluorouracil) can further improves survival benefit for patients with metastatic colorectal cancer(mCRC) compared to standard two-drug regimens in first-line therapy, especially when combined with bevacizumab. However, the increased toxicities of FOLFOXIRI limited its usage. Capecitabine demonstrates a superior efficacy and safety than fluorouracil, so we designed this trial to evaluate if the XELOXIRI plus bevacizumab can be a better alternative to FOLFOXIRI plus bevacizumab. The phase I study is to determine the safety and the recommended phase II dose (RP2D) of XELOXIRI plus Bevacizumab. In the phase II study, we aim to determine the efficacy of the regimen as first-line therapy for mCRC and explore potential molecular biomarkers (genomes, circulating tumor cell) for toxicity forecasting or efficacy monitoring.

Conditions

Metastatic Cancer; Colorectal Cancer; Colorectal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XELOXIRI/Bevacizumab

drugs: Irinotecan, Oxaliplatin, Capecitabine, Bevacizumab bevacizumab 5mg/kg on day1, irinotecan 150mg/m2 or 165mg/m2 on day1, oxaliplatin 85mg/m2 on day1 and capecitabine 1000mg/m2 twice a day on day1-7, administered every 2 week for 12 cycles, after 12 cycles, administer bevacizumab 5mg/kg on day 1 and capecitabine 1000mg/m2 twice a day on day1-7 as maintenance therapy.

Group Type: EXPERIMENTAL

XELOXIRI/Bevacizumab

Intervention Type: DRUG

bevacizumab 5mg/kg on day1, irinotecan 150mg/m2 or 165mg/m2 on day1, oxaliplatin 85mg/m2 on day1 and capecitabine 1000mg/m2 twice a day on day1-7 repeated every 2 week for 12 cycles, after 12 cycles, bevacizumab 5mg/kg on day 1 and capecitabine 1000mg/m2 twice a day on day1-7 as maintenance therapy repeated every 2 week

Interventions

XELOXIRI/Bevacizumab

bevacizumab 5mg/kg on day1, irinotecan 150mg/m2 or 165mg/m2 on day1, oxaliplatin 85mg/m2 on day1 and capecitabine 1000mg/m2 twice a day on day1-7 repeated every 2 week for 12 cycles, after 12 cycles, bevacizumab 5mg/kg on day 1 and capecitabine 1000mg/m2 twice a day on day1-7 as maintenance therapy repeated every 2 week

Intervention Type: DRUG

Other Intervention Names

Irinotecan, Oxaliplatin, Capecitabine, Bevacizumab

Eligibility Criteria

Inclusion Criteria

• Patients with histologically confirmed metastatic colorectal adenocarcinoma;
• Age 18-80 years old;
• Eastern Cooperation Oncology Group (ECOG) performance score(<2);
• At least one measurable lesion for disease assessment according to RECIST version 1.1;
• Able to take oral medications;
• Previous fluoropyrimidine-based adjuvant or neoadjuvant chemotherapy was allowed only when it ended ≥ 6 months before study enrollment;
• No previous therapy for mCRC;
• Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x109/L, absolute neutrophil count≥1.5x109/L, platelet count≥100x109/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤3x ULN; serum creatinine≤1.5x ULN; calculated creatinine clearance or 24 hour creatinine clearance ≥60ml/min.
• An expected survival of at least 3 months;
• Willingly provide written informed consent to study procedures.

Exclusion Criteria

• Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
• With a history of extensive enterotomy or pelvic radiation therapy; Suffering from grade 2 or higher symptomatic peripheral neuropathy according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
• Uncontrolled central nervous system metastasis, disseminated intravascular coagulation or active infection;
• With concurrent cancer distinct from colorectal adenocarcinoma except cured skin basal cell carcinoma and cervical carcinoma in situ;
• Undergone a major operation, open biopsy or major traumatic injury within 28 days before study enrollment or have potential to receive major operation during the trial;
• Received central venous access device within 2 days before study enrollment;
• Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascular accident, myocardial infarction, thromboembolism or hemorrhage within 6 months before enrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2 or uncontrolled hypertension.
• With positive urine protein and 24-hour urinary protein content>1g;
• Have a tendency of bleeding or clotting;
• With nasty open wounds, ulcers or fractures;
• Current or recent treatment of anticoagulants, antiplatelet agent or nonsteroidal anti-inflammatory drugs, while aspirin of daily dose less than 325mg is allowed.
• With any illness or medical conditions that may jeopardize the patient's compliance or interfere the analyses or judgements of study results;
• Pregnancy or lactation at the time of study entry;
• With fertility but refuse to contraception.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Lin Yang

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lin Yang

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences

Locations

National Center/Cancer Hospital, China Academy of Medical Science and Peking Union Medical College

Beijing, , China

Site Status: RECRUITING

National Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

M.D

Role: CONTACT

lyang69@sina.com

13681015148 ext. 13681015148

Facility Contacts

Lin Yang, M.D

Role: primary

lyang69@sina.com

13681015148 ext. 13681015148

Lin Yang, M.D

Role: primary

lyang69@sina.com

13681015148 ext. 13681015148

Other Identifiers

NCC2271

Identifier Type: -

Identifier Source: org_study_id