A Study of MEHD7945A and Cobimetinib (GDC-0973) in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01986166
First received: November 1, 2013
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

This open-label, multicenter, global Phase Ib study will evaluate the safety, to lerability and pharmacokinetics of MEHD7945A in combination with cobimetinib (GD C-0973) in patients with locally advanced or metastatic solid tumors that carry a KRAS mutation. The study comprises a dose-escalation and an indication-specifi c cohort expansion stage. Cohorts of patients will receive MEHD7945A intravenous ly every two weeks and escalating doses of oral cobimetinib for 21 consecutive d ays followed by 7 days off (28-day cycle). Study treatment may be continued unti l disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Neoplasms
Drug: MEHD7945A
Drug: cobimetinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE Ib, OPEN-LABEL, DOSE-ESCALATION STUDY OF THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MEHD7945A and GDC-0973 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS WITH MUTANT KRAS

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Safety: Incidence, nature and severity of adverse events [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • Safety: Incidence of anti-MEHD7945A antibodies [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • Safety: Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: MEHD7945A maximum serum concentrations (Cmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: MEHD7945A minimum serum concentrations (Cmin) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cobimetinib area under the concentration-time curve (AUC) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cobimetinib maximum plasma concentrations (Cmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to maximum cobimetinib plasma concentration (tmax) [ Time Frame: Cycles 1, 2 and 4 (up to 16 weeks) ] [ Designated as safety issue: No ]
  • Objective response, defined as a complete or partial response >/= 4 weeks after the initial documentation [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: November 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEHD7945A + cobimetinib Drug: MEHD7945A
Multiple doses IV
Drug: cobimetinib
Multiple escalating doses PO

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01986166

Contacts
Contact: Reference Study ID Number: GO29030 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
San Francisco, California, United States, 94115
United States, Colorado
Recruiting
Denver, Colorado, United States, 80262
United States, Connecticut
Not yet recruiting
New Haven, Connecticut, United States, 06520
United States, Michigan
Completed
Detroit, Michigan, United States, 48201
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37212
United States, Texas
Recruiting
Dallas, Texas, United States, 75390-8852
Spain
Recruiting
Barcelona, Spain, 08035
Recruiting
Madrid, Spain, 28050
Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01986166     History of Changes
Other Study ID Numbers: GO29030, 2013-001910-14
Study First Received: November 1, 2013
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on October 23, 2014