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Clinical Trial VICCPHI1387

Title

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of MEHD7945A and Cobimetinib in Patients with Locally Advanced or Metastatic Cancers with Mutant KRAS

Principal Investigator(s)

Jordan Berlin

Details

  • Protocol No. VICCPHI1387
  • Open Date: 05/28/2014
  • Staging: Phase I
  • Age Group: Adults
  • Scope: National
  • Objective: To evaluate the safety and tolerability of MEHD7945A and cobimetinib when administered in combination in patients with KRAS-mutant advanced or metastatic cancers. To identify the DLTs and to determine the MTD or tolerability at the maximum administered dose (MAD) of cobimetinib when administered in combination with MEHD7945A in patients with KRAS-mutant advanced or metastatic cancers. To identify a recommended Phase II dose (RP2D) and schedule for MEHD7945A and cobimetinib when administered in combination in patients with KRAS-mutant advanced or metastatic cancers.
  • Disease Sites: Phase I
  • Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: GDC-0973 (cobimetinib); MEHD7945A
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01986166
  • Secondary Protocol No: GO29030

Description

Patients are asked to take part in this research study because they have locally advanced or metastatic tumors that carry a mutation in the KRAS gene. Standard therapy for this type of tumor does not exist, has been shown to not work, or causes too many side effects. Genentech, Inc., a member of the Roche group, is the sponsor of this research study. This study is called Study GO29030. Genentech, the study sponsor, will pay the study center to cover the study center-s costs of conducting this research study. The purpose of this study is to find out what effect; good and/or bad, MEHD7945A and cobimetinib have on patients and their cancer, when they are combined together. The use of both MEHD7945A and cobimetinib in this research study is experimental. This means that MEHD7945A and cobimetinib have NOT been approved by the U.S. Food and Drug Administration (FDA) or other regulatory authorities for the treatment of cancer. MEHD7945A is a human antibody that is produced in cells. An antibody is a protein produced by the body-s immune system that binds other molecules. MEHD7945A is designed to bind and block two molecules present in many cancers: HER3 and EGFR. Cobimetinib is a small molecule that blocks a protein called MEK, which is part of the RAS signaling pathway within cells. Abnormal activation of this pathway occurs in many types of cancer. MEHD7945A and cobimetinib are being developed by the study sponsor (Genentech, Inc.) for the treatment of patients with cancer. The usefulness of combining these drugs in treating humans is not known. In laboratory studies, the combination of these drugs was more active in slowing the growth of cancer cells than either drug alone. Both MEHD7945A and cobimetinib have been given to patients with cancer before, but they have not been given together to humans before this study.

Eligibility

Ages Eligible for Study:18 Years and older
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No

Criteria

Inclusion Criteria:
• Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Evaluable disease or disease measurable per modified RECIST v1.1
• Consent to provide archival tumor tissue for biomarker testing
• Additionally, for patients who are considered for enrollment into the indication specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)
Exclusion Criteria:
• History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and EGFR inhibitor requiring discontinuation of treatment
• Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
• Allergy or hypersensitivity to components of the cobimetinib formulations
• History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
• History of interstitial lung disease (ILD)
• Known severe ulcer disease
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, CSCR, RVO, or neovascular macular degeneration.
Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
• Uncontrolled glaucoma with intraocular pressure >21 mmHg
• Grade >/= 3 hypertriglyceridemia.