Clinical trial NCT02141295: A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer
Official title: A Phase II, Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of RO5520985 (Vanucizumab) Plus FOLFOX Versus Bevacizumab Plus FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-05-19
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 multicenter, randomized, parallel arms, double-blind study of vanucizumab to evaluate the efficacy and safety of vanucizumab in combination with oxaliplatin, folinic acid, and 5-fluorouracil (5-FU) (mFOLFOX-6) versus bevacizumab (Avastin) + mFOLFOX-6 in participants with previously untreated metastatic colorectal cancer (mCRC). The study consists of 2 parts: a safety run-in open-label, single-arm part (Part 1) and a randomized, parallel-arms, double-blind part (Part 2). During Part 1 at least 6 eligible participants will receive 2000 milligrams (mg) vanucizumab every 2 weeks + mFOLFOX-6 in order to confirm the dose and schedule that will be used in Part 2. In Part 2, all eligible participants will be randomized in a ratio of 1:1 to receive either mFOLFOX-6 + vanucizumab or mFOLFOX-6 + bevacizumab. Study treatment (induction and maintenance) will be given on Day 1 of each 14-day cycle. Induction therapy will consist of up to 8 cycles of mFOLFOX-6 plus either bevacizumab or vanucizumab. Maintenance therapy will consist of 5-fluorouracil and folinic acid plus either vanucizumab or bevacizumab for up to 24 months or until disease progression, unacceptable toxicity, Investigator decision or consent withdrawal, whichever occurs first.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed mCRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
* Eastern Cooperative Oncology Group (World Health Organization) performance status of 0 or 1
* Adequate hematologic, liver, coagulation, renal, and cardiovascular function
* Recovery from all reversible AEs of previous medical therapies to baseline or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1, except for alopecia (any grade)
* Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (\< 2) years after the onset of menopause

Exclusion Criteria:

* Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, immunotherapy, hormonal therapy) before Day 1 of Cycle 1 for treatment of mCRC
* Malignancies other than CRC within 5 years prior to randomization, except for those with a minimal risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ treated surgically with curative intent
* Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior to Day 1 of Cycle 1
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle
* Pregnant or lactating women
* Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement
* Active infection requiring IV antibiotics
* Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of less than or equal to (\</=) 10 mg/day prednisone
* Sensory peripheral neuropathy greater than or equal to (\>/=) Grade 2
* Significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of Cycle 1
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation
* Current use of anticoagulants at therapeutic doses within 7 days prior to study drug administration. Prophylactic use of unfractioned heparin or low molecular weight heparin is permitted
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1
* History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis
* Colonic prosthesis (stent) implant in place
* History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation or intra abdominal abscess within 6 months prior to Day 1 of Cycle 1
* History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to Day 1 of Cycle 1
* Chronic daily treatment with NSAID (occasional use for the symptomatic relief of medical conditions, for example headache or fever is allowed)
* Chronic daily treatment with corticosteroids (dose \> 10 mg/day methylprednisolone equivalent) excluding inhaled steroids
* Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
* Metastatic disease that involve major airways or blood vessels, or centrally located mediastinal tumor masses (\< 30 millimeter from the carina) of large volume
* History of bronchopulmonary hemorrhage NCI CTCAE \>/= Grade 2 within 2 months prior to randomization
* Severe, nonhealing or open wound, active ulcer, or untreated bone fracture
* Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-FU toxicity
* Any other condition, diseases, metabolic dysfunction, active or uncontrolled infections/inflammation, physical examination finding, mental status or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates participation in the clinical study due to safety concerns, compliance with clinical study procedures or that may affect the interpretation of the results

Primary outcomes:
measure: Progression-free Survival (PFS), Time to Event
timeFrame: Baseline, every 8 weeks, up to approximately 29 months
Secondary outcomes:
measure: Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1
timeFrame: Baseline (within 28 days prior to Day 1), then every 8 weeks until progressive disease (PD), start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)
measure: Duration of Objective Response, as Assessed Using RECIST v. 1.1
timeFrame: Baseline (within 28 days prior to Day 1), then every 8 weeks until PD, start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)
measure: Overall Survival (OS)
timeFrame: Baseline until death from any cause (maximum up to approximately 3.5 years)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 29 months
measure: Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab
timeFrame: End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab
timeFrame: Cycles 1 and 8 of parts 1 and 2
measure: Maximum Observed Plasma Concentration (Cmax) of Vanucizumab
timeFrame: Cycles 1 and 8 of parts 1 and 2
measure: Minimum Observed Plasma Concentration (Clast) of Vanucizumab
timeFrame: Cycles 1 and 8 of parts 1 and 2
measure: Time to Reach Cmax (Tmax) of Vanucizumab
timeFrame: Cycles 1 and 8 of parts 1 and 2
measure: Plasma Terminal Half-Life (t1/2) of Vanucizumab
timeFrame: Cycle 8
measure: Plasma Clearance at Steady State (CLss) of Vanucizumab
timeFrame: Cycle 8
measure: Volume of Distribution at Steady State (Vss) of Vanucizumab
timeFrame: Cycle 8
measure: Cmax Accumulation Ratio (AR) of Vanucizumab
timeFrame: Cycle 8
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Ctr
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Associates for Research & Excellence, Inc.
state: California
city: Fresno
country: United States
facility: Fresno cCare
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Sepulveda
country: United States
facility: Va Greater Los Angeles Healthcare System
state: California
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Fort Worth
country: United States
facility: Ctr for Cancer and Blood Disorders
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre-Moorabbin Campus
state: Victoria
city: Salzburg
country: Austria
facility: Salzburger Landeskliniken LKH
city: Steyr
country: Austria
facility: Oö. Gesundheits- und Spitals-AG/LKH Steyr
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Angers Cedex 2
country: France
facility: Centre Paul Papin
city: Saint Herblain
country: France
facility: Institut De Cancerologie De L'Ouest; Medical Oncology
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Oncologia
city: Madrid
country: Spain
facility: HM Sanchinarro - CIOCC; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary; Medical Oncology Dept
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital; Oncology
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: