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Colorectal CancerPhase 2McCAVENCT02141295

A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer

A Phase 2 study testing 5-FU, Bevacizumab and Folinic acid in people with Colorectal Cancer, run by Hoffmann-La Roche at 39 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
5-FU, Bevacizumab and Folinic acid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
197 participants
Where
39 sitesin 7 countries
Study dates
30 Jun 2014to 1 Feb 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

39 sites in 7 countries.

39 sites in 7 countries

United States14 sites

  • Alabama Oncology

    Birmingham, Alabama, 35211

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • California Cancer Associates for Research & Excellence, Inc.

    Encinitas, California, 92008

  • SCRI Florida Cancer Specialists South

    Fort Myers, Florida, 33916

  • Ctr for Cancer and Blood Disorders

    Fort Worth, Texas, 76104

  • Fresno cCare

    Fresno, California, 93720

  • University of California San Diego Medical Center

    La Jolla, California, 92093-5354

  • Sarah Cannon Research Inst.

    Nashville, Tennessee, 37203

  • Ocala Oncology Center

    Ocala, Florida, 34471

  • Northern Utah Associates

    Ogden, Utah, 84403

  • Cancer Therapy & Research Center

    San Antonio, Texas, 78229

  • Va Greater Los Angeles Healthcare System

    Sepulveda, California, 91343

  • Arizona Clinical Research Ctr

    Tucson, Arizona, 85715

Other trials in United States

Spain12 sites

  • Hospital Universitario Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital del Mar; Servicio de Oncologia

    Barcelona, 08003

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Institut Catala d Oncologia Hospital Duran i Reynals

    Barcelona, 08908

  • Hospital Universitario Reina Sofia; Servicio de Oncologia

    Córdoba, Cordoba, 14004

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, 28007

  • Hospital Universitario Clínico San Carlos; Servicio de Oncologia

    Madrid, 28040

  • HM Sanchinarro - CIOCC; Servicio de Oncologia

    Madrid, 28050

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

United Kingdom5 sites

  • Aberdeen Royal Infirmary; Medical Oncology Dept

    Aberdeen, AB25 2ZN

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • Maidstone Hospital

    Maidstone, ME16 9QQ

  • Queen's Hospital; Oncology

    Romford, RM7 0AG

  • The Royal Marsden Hospital

    Sutton, SM2 5PT

Other trials in United Kingdom

Australia3 sites

  • Monash Medical Centre-Moorabbin Campus

    Clayton, Victoria, 3168

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • The Queen Elizabeth Hospital

    Woodville, South Australia, 5011

Other trials in Australia

Austria2 sites

  • Salzburger Landeskliniken LKH

    Salzburg, 5020

  • Oö. Gesundheits- und Spitals-AG/LKH Steyr

    Steyr, 4400

Other trials in Austria

France2 sites

  • Centre Paul Papin

    Angers, 49055

  • Institut De Cancerologie De L'Ouest; Medical Oncology

    Saint-Herblain, 44115

Other trials in France

Belgium1 site

  • Imeldaziekenhuis

    Bonheiden, 2820

Other trials in Belgium

About this study

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

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.

Being tested
5-FU, Bevacizumab, Folinic acid, Oxaliplatin, Vanucizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-FUDrug

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

  • BevacizumabDrug

    Also called Avastin

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

  • Folinic acidDrug

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

  • OxaliplatinDrug

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

  • VanucizumabDrug

    Also called RO5520985

    Vanucizumab will be administered according to dose and schedule described in respective arm.

Study groups in NCT02141295
Study groupRoleWhat they receive
Part 1 (Induction): Vanucizumab + mFOLFOX-6ExperimentalParticipants 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).
Receives: Drug: 5-FU; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Vanucizumab
Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acidExperimentalParticipants 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.
Receives: Drug: 5-FU; Drug: Folinic acid; Drug: Vanucizumab
Part 2 (Induction): Bevacizumab + mFOLFOX-6Active comparatorParticipants 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).
Receives: Drug: 5-FU; Drug: Bevacizumab; Drug: Folinic acid; Drug: Oxaliplatin
Part 2 (Induction): Vanucizumab + mFOLFOX-6ExperimentalParticipants 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).
Receives: Drug: 5-FU; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Vanucizumab
Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acidActive comparatorParticipants 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.
Receives: Drug: 5-FU; Drug: Bevacizumab; Drug: Folinic acid
Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acidExperimentalParticipants 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.
Receives: Drug: 5-FU; Drug: Folinic acid; Drug: Vanucizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS), Time to Event

    Efficacy of vanucizumab was evaluated in terms of PFS as Investigator-Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). PFS was defined as the time between randomization and the date of first documented disease progression or death from any cause on study, whichever occurred first. Death on study was defined as death from any cause within 30 days of the last study treatment.

    Measured: Baseline, every 8 weeks, up to approximately 29 months

Secondary outcomes (13)

  1. Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1

    Efficacy of vanucizumab was evaluated in terms of Percentage of Participants With ORR as Investigator-Assessed Using RECIST v. 1.1. Best Overall Confirmed Response.

    Measured: 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)

  2. Duration of Objective Response, as Assessed Using RECIST v. 1.1

    Efficacy of vanucizumab was evaluated in terms of duration of objective response as assessed using RECIST v. 1.1. This was computed using the PFS definition with death on study (deaths that occurred outside the 30 days window from the last study treatment are excluded).

    Measured: 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)

  3. Overall Survival (OS)

    Efficacy of vanucizumab was evaluated in terms of OS as the time from randomization until death from any cause. 99999 = data not estimable due to the low number of deaths.

    Measured: Baseline until death from any cause (maximum up to approximately 3.5 years)

  4. Percentage of Participants With Adverse Events (AEs)

    Safety is evaluated in terms of percentage of participants with at least one serious adverse event and percentage of participants with at least one adverse event.

    Measured: Up to approximately 29 months

  5. Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab

    Safety is evaluated in terms of number of participants with Human Anti-human Antibodies (HAHAs) Against Vanucizumab.

    Measured: End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)

  6. Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of AUC

    Measured: Cycles 1 and 8 of parts 1 and 2

  7. Maximum Observed Plasma Concentration (Cmax) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of Cmax

    Measured: Cycles 1 and 8 of parts 1 and 2

  8. Minimum Observed Plasma Concentration (Clast) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of Clast

    Measured: Cycles 1 and 8 of parts 1 and 2

  9. Time to Reach Cmax (Tmax) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of Tmax

    Measured: Cycles 1 and 8 of parts 1 and 2

  10. Plasma Terminal Half-Life (t1/2) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of t1/2, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

    Measured: Cycle 8

  11. Plasma Clearance at Steady State (CLss) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of CLss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

    Measured: Cycle 8

  12. Volume of Distribution at Steady State (Vss) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of Vss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

    Measured: Cycle 8

  13. Cmax Accumulation Ratio (AR) of Vanucizumab

    PK profile of vanucizumab was evaluated in terms of Cmax Ratio, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

    Measured: Cycle 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2014 (estimated)
  2. Study start30 Jun 2014
  3. Primary completion29 Jul 2016
  4. Study completion1 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
197 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02141295
Sponsor's protocol ID
BP29262
Other IDs
2013-005108-32
Acronym
McCAVE
Status last verified
Mar 2020
First submitted
15 May 2014
Last updated
25 Mar 2020
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 5-FU, Bevacizumab and Folinic acid in people with Colorectal Cancer, run by Hoffmann-La Roche at 39 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, Spain, United Kingdom, Australia, Austria and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS), Time to Event (time frame: Baseline, every 8 weeks, up to approximately 29 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02141295.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2020.

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