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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02141295




Registration number
NCT02141295
Ethics application status
Date submitted
15/05/2014
Date registered
19/05/2014
Date last updated
25/03/2020

Titles & IDs
Public title
A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer
Scientific 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
Secondary ID [1] 0 0
2013-005108-32
Secondary ID [2] 0 0
BP29262
Universal Trial Number (UTN)
Trial acronym
McCAVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-FU
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Folinic acid
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Vanucizumab

Experimental: Part 1 (Induction): Vanucizumab + mFOLFOX-6 - Participants will receive vanucizumab at a dose of 2000 milligram (mg) as intravenous (IV) infusion; oxaliplatin at a dose of 85 mg per meter-squared (mg/m^2) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Experimental: Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid - Participants will receive vanucizumab at a dose confirmed during induction as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Active Comparator: Part 2 (Induction): Bevacizumab + mFOLFOX-6 - Participants will receive bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Experimental: Part 2 (Induction): Vanucizumab + mFOLFOX-6 - Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Active Comparator: Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid - Participants will receive bevacizumab at a dose of 5 mg/kg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Experimental: Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid - Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.


Treatment: Drugs: 5-FU
5-FU will be administered according to dose and schedule described in respective arm.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered according to dose and schedule described in respective arm.

Treatment: Drugs: Folinic acid
Folinic acid will be administered according to dose and schedule described in respective arm.

Treatment: Drugs: Oxaliplatin
Oxaliplatin will be administered according to dose and schedule described in respective arm.

Treatment: Drugs: Vanucizumab
Vanucizumab will be administered according to dose and schedule described in respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS), Time to Event
Timepoint [1] 0 0
Baseline, every 8 weeks, up to approximately 29 months
Secondary outcome [1] 0 0
Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Duration of Objective Response, as Assessed Using RECIST v. 1.1
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Baseline until death from any cause (maximum up to approximately 3.5 years)
Secondary outcome [4] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [4] 0 0
Up to approximately 29 months
Secondary outcome [5] 0 0
Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab
Timepoint [5] 0 0
End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)
Secondary outcome [6] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab
Timepoint [6] 0 0
Cycles 1 and 8 of parts 1 and 2
Secondary outcome [7] 0 0
Maximum Observed Plasma Concentration (Cmax) of Vanucizumab
Timepoint [7] 0 0
Cycles 1 and 8 of parts 1 and 2
Secondary outcome [8] 0 0
Minimum Observed Plasma Concentration (Clast) of Vanucizumab
Timepoint [8] 0 0
Cycles 1 and 8 of parts 1 and 2
Secondary outcome [9] 0 0
Time to Reach Cmax (Tmax) of Vanucizumab
Timepoint [9] 0 0
Cycles 1 and 8 of parts 1 and 2
Secondary outcome [10] 0 0
Plasma Terminal Half-Life (t1/2) of Vanucizumab
Timepoint [10] 0 0
Cycle 8
Secondary outcome [11] 0 0
Plasma Clearance at Steady State (CLss) of Vanucizumab
Timepoint [11] 0 0
Cycle 8
Secondary outcome [12] 0 0
Volume of Distribution at Steady State (Vss) of Vanucizumab
Timepoint [12] 0 0
Cycle 8
Secondary outcome [13] 0 0
Cmax Accumulation Ratio (AR) of Vanucizumab
Timepoint [13] 0 0
Cycle 8

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2017
Sample size
Target
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 0 0
Monash Medical Centre-Moorabbin Campus - Clayton
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
Austria
State/province [10] 0 0
Salzburg
Country [11] 0 0
Austria
State/province [11] 0 0
Steyr
Country [12] 0 0
Belgium
State/province [12] 0 0
Bonheiden
Country [13] 0 0
France
State/province [13] 0 0
Angers Cedex 2
Country [14] 0 0
France
State/province [14] 0 0
Saint Herblain
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Cantabria
Country [17] 0 0
Spain
State/province [17] 0 0
Cordoba
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Spain
State/province [19] 0 0
Sevilla
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Aberdeen
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Maidstone
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Romford
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02141295
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02141295