A Study of Bevacizumab (Avastin) and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

A Multi-center, Open-label Clinical Trial to Evaluate the Objective Response Rate of Bevacizumab in Combination With Modified FOLFOX-6 Followed by One Year of Maintenance With Bevacizumab Alone in Patients With Initially Not or Borderline Resectable Colorectal Liver Metastases (The CLMO-001 Trial)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01383707
• Other study ID #: ML25625
• Secondary ID: 2011-001364-22
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 27, 2011
• Last updated: June 1, 2016
• Start date: August 2011
• Est. completion date: October 2016

Study information

• Verified date: June 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The multicenter, open-label, single-arm, non randomized, two-stage Simon's design, phase II study will evaluate the efficacy and safety of bevacizumab in combination with mFOLFOX-6 in participants with colorectal cancer and liver metastases. Participants will receive combination therapy of bevacizumab 5 milligrams per kilogram (mg/kg) intravenous (IV) dose and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil [5-FU] and oxaliplatin) every 2 weeks during Cycles 1-5 and Cycles 7-12. Participants will receive mFOLFOX-6 alone (without bevacizumab) on Cycle 6. In between Cycle 6 and 7, participants will undergo liver surgery if operable. Thereafter participants will receive bevacizumab (5 mg/kg IV every 2 weeks) alone for 52 weeks (26 cycles) after the end of the post-operative phase (maintenance therapy). At the end of the preoperative treatment phase (Cycles 1-6), participants showing different alternative conditions admitted by the protocol will undergo different management (alternative study designs 1 to 3).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 77
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult participants (male or female), greater than (>) 18 years of age

• Histologically confirmed adenocarcinoma of the colon or the rectum

• Primitive lesion is at a distance >12 centimeter (cm) from the anal margin for participants with primitive rectal tumour

• Measurable metastatic disease confined to the liver

• Eastern cooperative oncology group (ECOG) performance status 0-1

• No previous chemotherapy for metastatic disease or treatment with drugs targeting vascular endothelial growth factor receptor (VEGF) or epidermal growth factor receptor (EGFR)

• Adequate bone marrow, liver and renal function

• Urine analysis with proteinuria less than (<) 2+

• Use of at least one approved contraceptive method by participants with reproductive potential

• Written informed consent from the participants

• Surgical criteria for hepatic resection

• Adjuvant treatment (either only surgery on primitive tumour or surgery on primitive tumour + adjuvant chemotherapy) must have been concluded greater than or equal to (>/=) 6 months before enrolment

Exclusion Criteria:

• Presence of extrahepatic metastases

• Evidence of lomboaortic and celiac lymphnodes involvement

• Radiotherapy within 4 weeks before study start

• History of inflammatory bowel disease and/or acute/subacute bowel occlusion

• Presence of serious non-healing wound or ulcer

• Evidence of bleeding diathesis or coagulopathy

• Clinically significant cardiovascular disease

• Uncontrolled hypertension

• Current or recent ongoing treatment with anticoagulants

• Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration

• Treatment with any investigational drug within 30 days prior to enrolment

• Known allergy to chinese hamster ovary cell proteins, or any of the components of the study medications

• Co-existing malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. Interval between endoscopic biopsy or colorectal stenting and bevacizumab administration should be evaluated by oncologist/endoscopist

• Pregnant or lactating women

• Any other disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complication

• Participants with known Human immunodeficiency virus (HIV) infection

• Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection with concomitant cirrhosis or undergoing active treatment for the same

• Participants who are unable or unwilling to comply with the requirements of the protocol and follow-up procedures

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• 5-FU
Participants will receive 5-FU 400 mg per meter-squared (mg/m^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m^2, continuous infusion over 46 hours up to 12 cycles.
• Bevacizumab
Participants will receive 5 mg/kg bevacizumab IV dose on Day 1 of each 2 weeks' cycle up to Cycle 5 and thereafter cycles 7 to 12; followed by maintenance therapy of 5 mg/kg IV every 2 weeks up to 52 weeks (26 cycles).
• Levofolinic acid
Participants will receive levofolinic acid 200 mg/m^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.
• Oxaliplatin
Participants will receive oxaliplatin 85 mg/m^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with shrinkage (partial response) or disappearance of cancer (complete response)		Up to 11 cycles (2 weeks per cycle) of treatment	No
Secondary	Percentage of participants achieving no residual tumour (R0)/surgical margin with microscopic residual tumour (R1) liver resection		2 years	No
Secondary	Disease-free interval (DFI)		2 years	No
Secondary	Progression-free survival (PFS)		2 years	No
Secondary	Overall survival (OS)		2 years	No