Back to resultsA Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
5-Fluorouracil (5-FU)
Bevacizumab
Levofolinic acid
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility 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
Sites / Locations
- IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
- Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
- A.O. Universitaria Policlinico Di Modena; Ematologia
- Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia
- Irccs Ospedale San Raffaele;Oncologia Medica
- Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
- Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
- Fondazione IRCCS Policlinico San Matteo
- Ospedali Riuniti Di Ancona; Oncology
- Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
- Centro Catanese Di Oncologia; Oncologia Medica
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bevacizumab + mFOLFOX-6
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection
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).
Disease-free Interval (DFI)
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
Progression-Free Survival (PFS)
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.
Overall Survival (OS)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01383707
Brief Title
A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 12, 2011 (Actual)
Primary Completion Date
May 28, 2014 (Actual)
Study Completion Date
May 18, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab + mFOLFOX-6
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil (5-FU)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Levofolinic acid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
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 Measure Information:
Title
Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set
Description
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.
Time Frame
Up to 11 cycles of treatment (up to Week 22)
Title
Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)
Description
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.
Time Frame
Up to 11 cycles of treatment (up to Week 22)
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection
Description
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).
Time Frame
End of study up to approximately 3 years
Title
Disease-free Interval (DFI)
Description
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
Time Frame
End of study up to approximately 3 years
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
End of study up to approximately 3 years
Title
Overall Survival (OS)
Description
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
Time Frame
End of study up to approximately 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
A.O. Universitaria Policlinico Di Modena; Ematologia
City
Modena
State/Province
Emilia-Romagna
ZIP/Postal Code
41100
Country
Italy
Facility Name
Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia
City
Gallarate
State/Province
Lombardia
ZIP/Postal Code
21013
Country
Italy
Facility Name
Irccs Ospedale San Raffaele;Oncologia Medica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20141
Country
Italy
Facility Name
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Ospedali Riuniti Di Ancona; Oncology
City
Ancona
State/Province
Marche
ZIP/Postal Code
60121
Country
Italy
Facility Name
Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95122
Country
Italy
Facility Name
Centro Catanese Di Oncologia; Oncologia Medica
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95126
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
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