Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00996892
First received: October 12, 2009
Last updated: November 4, 2014
Last verified: November 2014
  Purpose

This is an open-label, multicenter, Phase Ib dose-escalation study designed to a ssess the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 a nd GDC-0941 administered in combination in patients with solid tumors.


Condition Intervention Phase
Solid Cancers
Drug: GDC-0941
Drug: GDC-0973/XL518
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Incidence and nature of dose-limiting toxicities [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
  • Incidence, nature and severity of adverse events and serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
  • PK parameters of GDC-0941 and GDC-0973 (total exposure, maximum plasma\n\nconcentration, and minimum concentration) [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response, duration of objective response, and progression-free survival (PFS) for patients with measurable disease according to RECIST [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]

Enrollment: 179
Study Start Date: November 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: GDC-0941
Repeating oral dose
Drug: GDC-0973/XL518
Repeating oral dose

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
  • Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
  • Life expectancy >= 12 weeks
  • Adequate hematologic and end organ function
  • Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

  • History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment
  • History of prior significant toxicity from another PI3K pathway inhibitor requiring discontinuation of treatment
  • Allergy or hypersensitivity to components of the GDC-0973 or GDC-0941 formulations
  • Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in Cycle 1
  • Experimental therapy within 4 weeks prior to first dose of study drug treatment in Cycle 1
  • Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
  • Prior anti-cancer therapy within 28 days before the first dose of study drug treatment in Cycle 1
  • History of diabetes requiring daily medication, or history of Grade >= 3 fasting hyperglycemia
  • Current severe, uncontrolled systemic disease
  • History of clinically significant cardiac or pulmonary dysfunction
  • History of malabsorption or other condition that would interfere with enteral absorption
  • Clinically significant history of liver disease (including cirrhosis), current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
  • Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics
  • Active autoimmune disease
  • Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
  • Pregnancy, lactation, or breastfeeding
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
  • No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays
  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: NCT00996892

Locations
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02114
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Iris Chan, M.D., Ph.D. Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00996892     History of Changes
Other Study ID Numbers: MEK4752g, GO01330
Study First Received: October 12, 2009
Last Updated: November 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
GDC0941
GDC0973
MEK
MEK Inhibitor
PI3K
PI3K Inhibitor
PI3 Kinase
PI3 Kinase Inhibitor

ClinicalTrials.gov processed this record on November 25, 2014