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NCT02141295: McCAVE

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

Terminated Phase 2 Results posted Last updated 25 March 2020
What this trial tests

Phase 2 trial testing 5-FU in Colorectal Cancer in 197 participants. Terminated before completion.

Timeline
30 June 2014
Primary endpoint
29 July 2016
1 February 2017

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment197
Start date30 June 2014
Primary completion29 July 2016
Estimated completion1 February 2017
Sites39 locations across France, Belgium, Austria, United Kingdom, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS), Time to Event Primary · Baseline, every 8 weeks, up to approximately 29 months

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.

GroupValue95% CI
Vanucizumab + mFOLFOX-6338.0312.0 – 381.0
Bevacizumab + mFOLFOX-6309.0284.0 – 352.0
Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1 Secondary · 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)

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.

GroupValue95% CI
Safety Run-In62.534.3 – 90.6
Vanucizumab + mFOLFOX-643.633.59 – 53.64
Bevacizumab + mFOLFOX-651.641.53 – 61.63
Duration of Objective Response, as Assessed Using RECIST v. 1.1 Secondary · 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)

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).

GroupValue95% CI
Vanucizumab + mFOLFOX-6342274 – 510
Bevacizumab + mFOLFOX-6304220 – 366
Overall Survival (OS) Secondary · Baseline until death from any cause (maximum up to approximately 3.5 years)

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.

GroupValue95% CI
Vanucizumab + mFOLFOX-6746.0687.0 – NA
Bevacizumab + mFOLFOX-6NA723.0 – NA
Percentage of Participants With Adverse Events (AEs) Secondary · Up to approximately 29 months

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.

Serious Adverse events
GroupValue95% CI
Safety Run-In37.5
Vanucizumab + mFOLFOX-649.5
Bevacizumab + mFOLFOX-643.2
Adverse events
GroupValue95% CI
Safety Run-In100
Vanucizumab + mFOLFOX-6100.0
Bevacizumab + mFOLFOX-6100.0
Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab Secondary · End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)

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

GroupValue95% CI
Safety Run-In2
Vanucizumab + mFOLFOX-61
Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab Secondary · Cycles 1 and 8 of parts 1 and 2

PK profile of vanucizumab was evaluated in terms of AUC

Cycle 1
GroupValue95% CI
Safety Run-In73600± 20.7
Vanucizumab + mFOLFOX-663500± 27.2
Cycle 8
GroupValue95% CI
Safety Run-In112000± 11.2
Vanucizumab + mFOLFOX-682100± 31.6
Maximum Observed Plasma Concentration (Cmax) of Vanucizumab Secondary · Cycles 1 and 8 of parts 1 and 2

PK profile of vanucizumab was evaluated in terms of Cmax

Cycle 1
GroupValue95% CI
Safety Run-In463± 18.5
Vanucizumab + mFOLFOX-6500± 26.3
Cycle 8
GroupValue95% CI
Safety Run-In685± 17.6
Vanucizumab + mFOLFOX-6794± 38.2
Minimum Observed Plasma Concentration (Clast) of Vanucizumab Secondary · Cycles 1 and 8 of parts 1 and 2

PK profile of vanucizumab was evaluated in terms of Clast

Cycle 1
GroupValue95% CI
Vanucizumab + mFOLFOX-6103± 67.2
Cycle 8
GroupValue95% CI
Vanucizumab + mFOLFOX-6361± 39.8
Time to Reach Cmax (Tmax) of Vanucizumab Secondary · Cycles 1 and 8 of parts 1 and 2

PK profile of vanucizumab was evaluated in terms of Tmax

Cycle 1
GroupValue95% CI
Safety Run-In2.791.50 – 7.67
Vanucizumab + mFOLFOX-62.051.0 – 26.1
Cycle 8
GroupValue95% CI
Safety Run-In4.040.5 – 5.25
Vanucizumab + mFOLFOX-61.580.5 – 4.77
Plasma Terminal Half-Life (t1/2) of Vanucizumab Secondary · Cycle 8

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.

GroupValue95% CI
Safety Run-In202± 12.4
Vanucizumab + mFOLFOX-6157± 30.3
Plasma Clearance at Steady State (CLss) of Vanucizumab Secondary · Cycle 8

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.

GroupValue95% CI
Safety Run-In15.3± 26.7
Vanucizumab + mFOLFOX-618.0± 29.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 28 days after the last dose of study drug (maximum treatment time = approximately 29 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Safety Run-In
Serious: 3/8 (38%)
Deaths: 3/8
Vanucizumab + mFOLFOX-6
Serious: 46/93 (49%)
Deaths: 24/93
Bevacizumab + mFOLFOX-6
Serious: 41/95 (43%)
Deaths: 27/95

Serious adverse events (90 terms)

ReactionSystemSafety Run-InVanucizumab + mFOLFOX-6Bevacizumab + mFOLFOX-6
Febrile NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Large intestine perforationGastrointestinal disorders
SubileusGastrointestinal disorders
PneumoniaInfections and infestations
NeutropeniaBlood and lymphatic system disorders
Gastrointestinal perforationGastrointestinal disorders
Septic shockInfections and infestations
Transient ischaemic attackNervous system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Angina unstableCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac arrestCardiac disorders
Cardiac disorderCardiac disorders
Cardiac failureCardiac disorders
Coronary artery diseaseCardiac disorders
Myocardial IschaemiaCardiac disorders
Other adverse events (97 terms — click to expand)

ReactionSystemSafety Run-InVanucizumab + mFOLFOX-6Bevacizumab + mFOLFOX-6
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
HypertensionVascular disorders
Decreased appetiteMetabolism and nutrition disorders
Peripheral sensory neuropathyNervous system disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Mucosal inflammationGeneral disorders
Neuropathy peripheralNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
FatigueGeneral disorders
DysaesthesiaNervous system disorders
DysgeusiaNervous system disorders
Infusion related reactionInjury, poisoning and procedural complications
HeadacheNervous system disorders
PyrexiaGeneral disorders
ParaesthesiaNervous system disorders
Back painMusculoskeletal and connective tissue disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
StomatitisGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
AlopeciaSkin and subcutaneous tissue disorders
Weight decreasedInvestigations
DysphoniaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
ProteinuriaRenal and urinary disorders
DyspepsiaGastrointestinal disorders
Oedema peripheralGeneral disorders
Temperature intoleranceGeneral disorders
Urinary tract infectionInfections and infestations
Platelet count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Febrile Neutropenia, Pyrexia, Urinary tract infection, Abdominal pain, Diarrhoea, Intestinal obstruction, Intestinal perforation, Large intestine perforation.

Data from ClinicalTrials.gov NCT02141295 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges.
    Fukumura D, Kloepper J, Amoozgar Z, Duda DG, et al · · 2018 · cited 1560× · PMID 29508855 · DOI 10.1038/nrclinonc.2018.29
  2. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  3. Emerging new therapeutic antibody derivatives for cancer treatment.
    Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
  4. Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival.
    Kloepper J, Riedemann L, Amoozgar Z, Seano G, et al · · 2016 · cited 296× · PMID 27044098 · DOI 10.1073/pnas.1525360113
  5. The use of CrossMAb technology for the generation of bi- and multispecific antibodies.
    Klein C, Schaefer W, Regula JT. · · 2016 · cited 126× · PMID 27285945 · DOI 10.1080/19420862.2016.1197457
  6. A Review of Anti-Angiogenic Targets for Monoclonal Antibody Cancer Therapy.
    Kong DH, Kim MR, Jang JH, Na HJ, et al · · 2017 · cited 111× · PMID 28817103 · DOI 10.3390/ijms18081786
  7. Biology drives the discovery of bispecific antibodies as innovative therapeutics.
    Nie S, Wang Z, Moscoso-Castro M, D'Souza P, et al · · 2020 · cited 79× · PMID 33928225 · DOI 10.1093/abt/tbaa003
  8. Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer.
    Elshiaty M, Schindler H, Christopoulos P. · · 2021 · cited 71× · PMID 34073188 · DOI 10.3390/ijms22115632

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02141295.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing