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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01974258
• Other study ID #: GO29026
• Status: Withdrawn
• Phase: Phase 1
• First received: October 28, 2013
• Last updated: November 1, 2016
• Start date: February 2014
• Est. completion date: July 2014

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Cobimetinib
Escalating dose
• Cobimetinib
Orally administered once daily for 21 consecutive days, followed by 7 days off.
• Onartuzumab
Administered by IV infusion every 2 weeks
• Vemurafenib
Orally administered twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of dose-limiting toxicities (DLTs) of vermurafenib and/or cobimetinib used in combination with onartuzumab.		24 to 36 months	Yes
Primary	Safety: Incidence of anti-therapeutic antibodies against onartuzumab.		24 to 36 months	No
Primary	Safety: Incidence of adverse events (AE)		24 to 36 months	No
Secondary	Pharmacokinetics: Maximum concentration (Cmax) of onartuzumab		24 to 36 months	No
Secondary	Pharmacokinetics: Maximum concentration (Cmax) of cobimetinib		24 to 36 months	No
Secondary	Pharmacokinetics: Maximum concentration (Cmax) of vemurafenib		24 to 36 months	No
Secondary	Efficacy: Overall response rate		24 to 36 months	No
Secondary	Efficacy: Progression-free survival		24 to 36 months	No
Secondary	Efficacy: Duration of response		24 to 36 months	No
Secondary	Efficacy: Overall survival		24 to 36 months	No