Clinical trial NCT01383707: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-06-28
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set
timeFrame: Up to 11 cycles of treatment (up to Week 22)
measure: Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)
timeFrame: Up to 11 cycles of treatment (up to Week 22)
Secondary outcomes:
measure: Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection
timeFrame: End of study up to approximately 3 years
measure: Disease-free Interval (DFI)
timeFrame: End of study up to approximately 3 years
measure: Progression-Free Survival (PFS)
timeFrame: End of study up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: End of study up to approximately 3 years
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
state: Emilia-Romagna
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena; Ematologia
state: Emilia-Romagna
city: Gallarate
country: Italy
facility: Azienda Ospedaliera Sant' Antonio Abate; Divisione di Oncologia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
state: Lombardia
city: Ancona
country: Italy
facility: Ospedali Riuniti Di Ancona; Oncology
state: Marche
city: Catania
country: Italy
facility: Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
state: Sicilia
city: Catania
country: Italy
facility: Centro Catanese Di Oncologia; Oncologia Medica
state: Sicilia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: