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

NCT01974258 | Withdrawn Phase 1

• 1 other identifier: GO29026
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• Safety: Incidence of dose-limiting toxicities (DLTs) of vermurafenib and/or cobimetinib used in combination with onartuzumab.

  24 to 36 months

• Safety: Incidence of anti-therapeutic antibodies against onartuzumab.

  24 to 36 months

• Safety: Incidence of adverse events (AE)

  24 to 36 months

Secondary Outcomes (7)

• Pharmacokinetics: Maximum concentration (Cmax) of onartuzumab

  24 to 36 months

• Pharmacokinetics: Maximum concentration (Cmax) of cobimetinib

  24 to 36 months

• Pharmacokinetics: Maximum concentration (Cmax) of vemurafenib

  24 to 36 months

• Efficacy: Overall response rate

  24 to 36 months

• Efficacy: Progression-free survival

  24 to 36 months

Study Arms (4)

Dose-expansion: onartuzumab + cobimetinib

EXPERIMENTAL

Drug: Cobimetinib; Drug: Onartuzumab

Dose-expansion: onartuzumab + vemurafenib

EXPERIMENTAL

Drug: Onartuzumab; Drug: Vemurafenib

Dose-expansion: onartuzumab + vemurafenib + cobimetinib

EXPERIMENTAL

Drug: Cobimetinib; Drug: Onartuzumab; Drug: Vemurafenib

Dose-finding: onartuzumab + vemurafenib + cobimetinib

EXPERIMENTAL

Drug: Cobimetinib; Drug: Onartuzumab; Drug: Vemurafenib

Interventions

Cobimetinib DRUG

Escalating dose

Dose-finding: onartuzumab + vemurafenib + cobimetinib

Onartuzumab DRUG

Administered by IV infusion every 2 weeks

Dose-expansion: onartuzumab + cobimetinib; Dose-expansion: onartuzumab + vemurafenib; Dose-expansion: onartuzumab + vemurafenib + cobimetinib; Dose-finding: onartuzumab + vemurafenib + cobimetinib

Vemurafenib DRUG

Orally administered twice daily

Dose-expansion: onartuzumab + vemurafenib; Dose-expansion: onartuzumab + vemurafenib + cobimetinib; Dose-finding: onartuzumab + vemurafenib + cobimetinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Unknown Facility

Los Angeles, California, 90025, United States

Location

Unknown Facility

Sarasota, Florida, 34232, United States

Location

Unknown Facility

Detroit, Michigan, 48201, United States

Location

Unknown Facility

Canton, Ohio, 44718, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73104, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

cobimetinib; onartuzumab; Vemurafenib

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 1, 2013
• Study Start: February 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (6)