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Safety, Tolerability, and Pharmacokinetics of Onartuzumab Combined With Vemurafenib and/or Cobimetinib in Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01974258
Recruitment Status : Withdrawn
First Posted : November 1, 2013
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 28, 2013
First Posted Date  ICMJE November 1, 2013
Last Update Posted Date November 2, 2016
Study Start Date  ICMJE February 2014
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
  • Safety: Incidence of dose-limiting toxicities (DLTs) of vermurafenib and/or cobimetinib used in combination with onartuzumab. [ Time Frame: 24 to 36 months ]
  • Safety: Incidence of anti-therapeutic antibodies against onartuzumab. [ Time Frame: 24 to 36 months ]
  • Safety: Incidence of adverse events (AE) [ Time Frame: 24 to 36 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
  • Pharmacokinetics: Maximum concentration (Cmax) of onartuzumab [ Time Frame: 24 to 36 months ]
  • Pharmacokinetics: Maximum concentration (Cmax) of cobimetinib [ Time Frame: 24 to 36 months ]
  • Pharmacokinetics: Maximum concentration (Cmax) of vemurafenib [ Time Frame: 24 to 36 months ]
  • Efficacy: Overall response rate [ Time Frame: 24 to 36 months ]
  • Efficacy: Progression-free survival [ Time Frame: 24 to 36 months ]
  • Efficacy: Duration of response [ Time Frame: 24 to 36 months ]
  • Efficacy: Overall survival [ Time Frame: 24 to 36 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Pharmacokinetics of Onartuzumab Combined With Vemurafenib and/or Cobimetinib in Cancer Patients
Official Title  ICMJE A PHASE Ib, OPEN-LABEL STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ONARTUZUMAB IN COMBINATION WITH VEMURAFENIB AND/OR COBIMETINIB IN PATIENTS WITH ADVANCED SOLID MALIGNANCIES
Brief Summary This study will evaluate the maximum tolerated dose and dose-limiting toxicities of vemurafenib and/or cobimetinib when used with onartuzumab in cancer patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: Cobimetinib
    Escalating dose
  • Drug: Cobimetinib
    Orally administered once daily for 21 consecutive days, followed by 7 days off.
  • Drug: Onartuzumab
    Administered by IV infusion every 2 weeks
  • Drug: Vemurafenib
    Orally administered twice daily
Study Arms  ICMJE
  • Experimental: Dose-expansion: onartuzumab + cobimetinib
    Interventions:
    • Drug: Cobimetinib
    • Drug: Onartuzumab
  • Experimental: Dose-expansion: onartuzumab + vemurafenib
    Interventions:
    • Drug: Onartuzumab
    • Drug: Vemurafenib
  • Experimental: Dose-expansion: onartuzumab + vemurafenib + cobimetinib
    Interventions:
    • Drug: Cobimetinib
    • Drug: Onartuzumab
    • Drug: Vemurafenib
  • Experimental: Dose-finding: onartuzumab + vemurafenib + cobimetinib
    Interventions:
    • Drug: Cobimetinib
    • Drug: Onartuzumab
    • Drug: Vemurafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 1, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2013)
96
Estimated Study Completion Date  ICMJE July 2014
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients >/= 18 years of age.
  • Patients with histologically confirmed, BRAFV600-mutant, unresectable, locally advanced or metastatic solid malignancies. OR
  • Patients with a histologically confirmed, KRAS-mutant, Stage IV colorectal adenocarcinoma, or KRAS-mutant metastatic non-small-cell lung carcinoma. OR
  • Patients with histologically confirmed BRAFV600-mutant unresectable Stage IIIC or Stage IV metastatic melanoma.
  • Valid MET IHC test result.
  • Measurable disease per Response Evaluation Criteria in Solid Tumors v1.1
  • ECOG performance status of 0 or 1.
  • For BRAFV600-mutant cancers:
  • Previously untreated for their melanoma or previously treated for their melanoma but without prior exposure to any HGF, MET, BRAF, or MEK inhibitor therapy
  • BRAFV600-mutant solid malignancies other than melanoma for which standard therapy does not exist has proven to be ineffective or intolerable or is considered inappropriate.

Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.

  • For KRAS-mutant cancers:
  • mCRC patients must have received therapeutic regimens including oxaliplatin, irinotecan, 5-FU, and bevacizumab, or determined to be ineligible for these treatments. Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
  • Metastatic NSCLC patients must have received platinum-based doublet chemotherapy or determined to be ineligible for this regimen. Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
  • Consent to provide tumor tissue for biomarker analyses.
  • Life expectancy >/= 12 weeks.
  • Fully recovery from the effects of any major surgery or significant traumatic injury within 14 days from the first dose of study treatment.
  • Adequate hematologic and end organ function, as defined by clinical laboratory results.
  • Use of effective form(s) of contraception as defined by protocol during the course of this study and for at least 6 months after study drug discontinuation.

Exclusion Criteria:

  • Palliative radiotherapy or experimental therapy within 28 days prior to first dose of study drug treatment.
  • Major surgical procedure or significant traumatic injury from 28 days prior to first dose of study drug treatment until end of study.
  • History of another malignancy in the previous 5 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated cervical carcinoma in situ, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer that has been treated surgically and is presumed cured, or other malignancies with an expected curative outcome.
  • Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated central nervous system (CNS) metastases or spinal cord compression without evidence of clinically stable disease for more than 14 days.

Note: Patients with treated CNS metastases who are asymptomatic and on a stable dose of corticosteroids for more than 14 days prior to Cycle 1 Day 1 are eligible.

  • For patients given cobimetinib: Evidence of visible retinal pathology that is considered a risk factor for neurosensory detachment, retinal vein occlusion, or neovascular macular degeneration, or of conditions that are risk factors for retinal vein occlusion.
  • Current or history of clinically significant cardiac or pulmonary dysfunction.
  • Lack of recovery to Grade 1 or better from adverse events due to investigational or other agents administered more than 28 days prior to enrollment, except for alopecia.
  • Current severe, uncontrolled systemic disease.
  • Inability or unwillingness to swallow pills.
  • History of malabsorption or other condition that would interfere with gastrointestinal absorption of study drug.
  • History of clinically significant liver disease, current alcohol abuse, or known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).
  • Severe (Grade 3 and above) active infection at enrollment, or other serious underlying medical conditions.
  • Required medication known to cause edema and/or cardiac failure.
  • Active autoimmune disease.
  • Uncontrolled ascites requiring weekly, large-volume paracentesis for 3 consecutive weeks prior to enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01974258
Other Study ID Numbers  ICMJE GO29026
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP