ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01383707
Recruitment Status : Completed
First Posted : June 28, 2011
Results First Posted : September 7, 2016
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: 5-Fluorouracil (5-FU) Drug: Bevacizumab Drug: Levofolinic acid Drug: Oxaliplatin Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 12, 2011
Actual Primary Completion Date : May 28, 2014
Actual Study Completion Date : May 18, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: Bevacizumab + mFOLFOX-6
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)
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.

Drug: 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).
Other Name: Avastin

Drug: 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.

Drug: 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.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set [ Time Frame: Up to 11 cycles of treatment (up to Week 22) ]
    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.

  2. Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS) [ Time Frame: Up to 11 cycles of treatment (up to Week 22) ]
    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.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection [ Time Frame: End of study up to approximately 3 years ]
    The percentage of participants achieving R0/R1 liver resection was defined as the percentage of participants achieving R0 surgery (no residual tumor) plus percentage of participants achieving R1 surgery (surgical margin with microscopic residual tumor).

  2. Disease-free Interval (DFI) [ Time Frame: End of study up to approximately 3 years ]
    DFI was defined as the time from the date of R0/R1 surgery to the date of disease relapse or death due to any cause. Participants who did not progress were considered censored at the date of the last assessment performed. For participants receiving two-stage resection, the date of R0/R1 surgery was the date of the second surgery. Participants, who did not receive surgery and participants without R0/R1 surgery were censored at Day 1. DFI was calculated as follows: DFI (months) = ([Date of R0/R1 surgery ‐ Date of 1st relapse/Death] + 1)/30

  3. Progression-Free Survival (PFS) [ Time Frame: End of study up to approximately 3 years ]
    PFS was defined as the time from the date of first study drug administration to the date of disease progression or death due to any cause, whichever came first. Progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants, who did not progress were censored at the date of the last assessment performed. Participants who withdrew from the study without documented progression and for whom an electronic case report form (eCRF) existed as evidence that evaluations had been made, were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessments, but known to be alive were censored at the time of first study drug administration. PFS was calculated: PFS (months) = ([Date of Event - Date of first study drug administration] + 1)/30.

  4. Overall Survival (OS) [ Time Frame: End of study up to approximately 3 years ]
    OS was defined as the time from the date of first study drug administration to the date of death due to any cause. Participants who were alive at the time of the analysis were censored at the last date the participant was known to be alive. OS was calculated as follows: OS (months) = ([Date of Death - first study drug administration] + 1)/30



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01383707


Locations
Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
Napoli, Campania, Italy, 80131
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
Bologna, Emilia-Romagna, Italy, 40138
A.O. Universitaria Policlinico Di Modena; Ematologia
Modena, Emilia-Romagna, Italy, 41100
Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia
Gallarate, Lombardia, Italy, 21013
Irccs Ospedale San Raffaele;Oncologia Medica
Milano, Lombardia, Italy, 20132
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
Milano, Lombardia, Italy, 20141
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milano, Lombardia, Italy, 20162
Fondazione IRCCS Policlinico San Matteo
Pavia, Lombardia, Italy, 27100
Ospedali Riuniti Di Ancona; Oncology
Ancona, Marche, Italy, 60121
Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
Catania, Sicilia, Italy, 95122
Centro Catanese Di Oncologia; Oncologia Medica
Catania, Sicilia, Italy, 95126
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01383707     History of Changes
Other Study ID Numbers: ML25625
2011-001364-22 ( EudraCT Number )
First Posted: June 28, 2011    Key Record Dates
Results First Posted: September 7, 2016
Last Update Posted: June 14, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Fluorouracil
Leucovorin
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex