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

NCT01383707 | Completed Phase 2 Results

• 2 other identifiers: ML256252011-001364-22
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 11

Brief Summary

The multicenter, open-label, single-arm, non-randomized, two-stage Simon's design, phase II study (The CLMO-001 Trial) will evaluate the efficacy and safety of bevacizumab in combination with mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\] and oxaliplatin) 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 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).

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set

  ORR was defined as the percentage of participants with shrinkage (partial response \[PR\]) or disappearance of cancer (complete response \[CR\]). Tumor response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 11 cycles of treatment (up to Week 22)

• Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)

  ORR was defined as the percentage of participants with shrinkage (PR) or disappearance of cancer (CR). Tumor response was evaluated according to the RECIST v1.1. The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of CT scan (abdomen + pelvis + chest) or CE-MRI (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.

  Up to 11 cycles of treatment (up to Week 22)

Secondary Outcomes (4)

• Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection

  End of study up to approximately 3 years

• Disease-free Interval (DFI)

  End of study up to approximately 3 years

• Progression-Free Survival (PFS)

  End of study up to approximately 3 years

• Overall Survival (OS)

  End of study up to approximately 3 years

Study Arms (1)

Bevacizumab + mFOLFOX-6

EXPERIMENTAL

Participants will receive combination therapy of bevacizumab 5 mg/kg IV dose and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy).

Drug: 5-Fluorouracil (5-FU); Drug: Bevacizumab; Drug: Levofolinic acid; Drug: Oxaliplatin

Interventions

5-Fluorouracil (5-FU) DRUG

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 + mFOLFOX-6

Bevacizumab DRUG

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).

Also known as: Avastin

Bevacizumab + mFOLFOX-6

Levofolinic acid DRUG

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.

Bevacizumab + mFOLFOX-6

Oxaliplatin DRUG

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.

Bevacizumab + mFOLFOX-6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 tumor
• 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 tumor or surgery on primitive tumor + adjuvant chemotherapy) must have been concluded greater than or equal to (\>/=) 6 months before enrollment

You may not qualify if:

• Presence of extrahepatic metastases
• Evidence of lumbo-aortic and celiac lymph nodes involvement
• Radiotherapy within 4 weeks before study start
• History of inflammatory bowel disease and/or acute/sub-acute 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 enrollment
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

Location

A.O. Universitaria Policlinico Di Modena; Ematologia

Modena, Emilia-Romagna, 41100, Italy

Location

Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia

Gallarate, Lombardy, 21013, Italy

Location

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, 20132, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milan, Lombardy, 20141, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, 20162, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica

Catania, Sicily, 95122, Italy

Location

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicily, 95126, Italy

Location

Ospedali Riuniti Di Ancona; Oncology

Ancona, The Marches, 60121, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Bevacizumab; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2011
• First Posted: June 28, 2011
• Study Start: August 12, 2011
• Primary Completion: May 28, 2014
• Study Completion: May 18, 2016
• Last Updated: June 14, 2017
• Results First Posted: September 7, 2016

Record last verified: 2017-05

Locations

IT (11)