Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02141295
Other study ID # BP29262
Secondary ID 2013-005108-32
Status Terminated
Phase Phase 2
First received
Last updated
Start date June 30, 2014
Est. completion date February 1, 2017

Study information

Verified date March 2020
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.


Recruitment information / eligibility

Status Terminated
Enrollment 197
Est. completion date February 1, 2017
Est. primary completion date July 29, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
5-FU
5-FU will be administered according to dose and schedule described in respective arm.
Bevacizumab
Bevacizumab will be administered according to dose and schedule described in respective arm.
Folinic acid
Folinic acid will be administered according to dose and schedule described in respective arm.
Oxaliplatin
Oxaliplatin will be administered according to dose and schedule described in respective arm.
Vanucizumab
Vanucizumab will be administered according to dose and schedule described in respective arm.

Locations

Country Name City State
Australia Monash Medical Centre-Moorabbin Campus Clayton Victoria
Australia Calvary Mater Newcastle Waratah New South Wales
Australia The Queen Elizabeth Hospital Woodville South Australia
Austria Salzburger Landeskliniken LKH Salzburg
Austria Oö. Gesundheits- und Spitals-AG/LKH Steyr Steyr
Belgium Imeldaziekenhuis Bonheiden
France Centre Paul Papin Angers Cedex 2
France Institut De Cancerologie De L'Ouest; Medical Oncology Saint Herblain
Spain Hospital Universitario Germans Trias i Pujol Badalona Barcelona
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital del Mar; Servicio de Oncologia Barcelona
Spain Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona
Spain Institut Catala d Oncologia Hospital Duran i Reynals Barcelona
Spain Hospital Universitario Reina Sofia; Servicio de Oncologia Córdoba Cordoba
Spain HM Sanchinarro - CIOCC; Servicio de Oncologia Madrid
Spain Hospital General Universitario Gregorio Marañon; Servicio de Oncologia Madrid
Spain Hospital Universitario Clínico San Carlos; Servicio de Oncologia Madrid
Spain Hospital Universitario Marques de Valdecilla Santander Cantabria
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Hospital Clinico Universitario de Valencia Valencia
United Kingdom Aberdeen Royal Infirmary; Medical Oncology Dept Aberdeen
United Kingdom Guys and St Thomas NHS Foundation Trust, Guys Hospital London
United Kingdom Maidstone Hospital Maidstone
United Kingdom Queen's Hospital; Oncology Romford
United Kingdom The Royal Marsden Hospital Sutton
United States Alabama Oncology Birmingham Alabama
United States Oncology Hematology Care Inc Cincinnati Ohio
United States Duke University Medical Center Durham North Carolina
United States California Cancer Associates for Research & Excellence, Inc. Encinitas California
United States SCRI Florida Cancer Specialists South Fort Myers Florida
United States Ctr for Cancer and Blood Disorders Fort Worth Texas
United States Fresno cCare Fresno California
United States University of California San Diego Medical Center La Jolla California
United States Sarah Cannon Research Inst. Nashville Tennessee
United States Ocala Oncology Center Ocala Florida
United States Northern Utah Associates Ogden Utah
United States Cancer Therapy & Research Center San Antonio Texas
United States Va Greater Los Angeles Healthcare System Sepulveda California
United States Arizona Clinical Research Ctr Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Baseline, every 8 weeks, up to approximately 29 months
Secondary 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. 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 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). 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 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. Baseline until death from any cause (maximum up to approximately 3.5 years)
Secondary 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. Up to approximately 29 months
Secondary 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. End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)
Secondary Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab PK profile of vanucizumab was evaluated in terms of AUC Cycles 1 and 8 of parts 1 and 2
Secondary Maximum Observed Plasma Concentration (Cmax) of Vanucizumab PK profile of vanucizumab was evaluated in terms of Cmax Cycles 1 and 8 of parts 1 and 2
Secondary Minimum Observed Plasma Concentration (Clast) of Vanucizumab PK profile of vanucizumab was evaluated in terms of Clast Cycles 1 and 8 of parts 1 and 2
Secondary Time to Reach Cmax (Tmax) of Vanucizumab PK profile of vanucizumab was evaluated in terms of Tmax Cycles 1 and 8 of parts 1 and 2
Secondary 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. Cycle 8
Secondary 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. Cycle 8
Secondary 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. Cycle 8
Secondary 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. Cycle 8
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Active, not recruiting NCT05551052 - CRC Detection Reliable Assessment With Blood
Completed NCT00098787 - Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer Phase 2
Recruiting NCT06037954 - A Study of Mental Health Care in People With Cancer N/A
Recruiting NCT05425940 - Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer Phase 3
Suspended NCT04595604 - Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery. N/A
Completed NCT03414125 - Effect of Mailed Invites of Choice of Colonoscopy or FIT vs. Mailed FIT Alone on Colorectal Cancer Screening N/A
Completed NCT02963831 - A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies Phase 1/Phase 2
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Terminated NCT01847599 - Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib N/A
Completed NCT05799976 - Text Message-Based Nudges Prior to Primary Care Visits to Increase Care Gap Closure N/A
Recruiting NCT03874026 - Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT03181334 - The C-SPAN Coalition: Colorectal Cancer Screening and Patient Navigation N/A
Completed NCT03167125 - Participatory Research to Advance Colon Cancer Prevention N/A
Recruiting NCT04258137 - Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study N/A
Recruiting NCT05568420 - A Study of the Possible Effects of Medication on Young Onset Colorectal Cancer (YOCRC)
Recruiting NCT02972541 - Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer N/A
Completed NCT02876224 - Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors Phase 1
Completed NCT01943500 - Collection of Blood Specimens for Circulating Tumor Cell Analysis N/A