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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
77
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).
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.
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
Naples, Campania, Italy
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
Bologna, Emilia-Romagna, Italy
A.O. Universitaria Policlinico Di Modena; Ematologia
Modena, Emilia-Romagna, Italy
Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia
Gallarate, Lombardy, Italy
Irccs Ospedale San Raffaele;Oncologia Medica
Milan, Lombardy, Italy
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
Milan, Lombardy, Italy
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milan, Lombardy, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, Lombardy, Italy
Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
Catania, Sicily, Italy
Centro Catanese Di Oncologia; Oncologia Medica
Catania, Sicily, Italy
...and 1 more locations
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.
Time frame: 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.
Time frame: Up to 11 cycles of treatment (up to Week 22)
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).
Time frame: End of study up to approximately 3 years
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
Time frame: End of study up to approximately 3 years
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.
Time frame: End of study up to approximately 3 years
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
Time frame: End of study up to approximately 3 years
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