A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT01383707|
Recruitment Status : Completed
First Posted : June 28, 2011
Results First Posted : September 7, 2016
Last Update Posted : June 14, 2017
|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)|
|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|
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.
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.
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.
- 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.
- 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.
- 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).
- 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
- 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.
- 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
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
|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|
|Study Director:||Clinical Trials||Hoffmann-La Roche|