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A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01875705
First received: June 10, 2013
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
This is an open-label, multicenter, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0994 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) or the subsequent expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0994 administered daily. Stage II will gather additional data on safety, tolerability, and pharmacokinetics of the recommended dose of GDC-0994 determined in Stage I.

Condition Intervention Phase
Solid Tumor
Drug: GDC-0994
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Official Title: An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: Approximately 2 years ]
  • Maximum tolerated dose [ Time Frame: Approximately 2 years ]
  • Dose-limiting toxicities [ Time Frame: Approximately 2 years ]
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: Approximately 2 years ]
  • Pharmacokinetics: Maximum plasma concentrations [ Time Frame: Approximately 2 years ]
  • Pharmacokinetics: Minimum plasma concentrations [ Time Frame: Approximately 2 years ]
  • Pharmacokinetics: Time to maximum plasma concentration [ Time Frame: Approximately 2 years ]
  • Pharmacokinetics: Apparent terminal elimination half-life [ Time Frame: Approximately 2 years ]

Secondary Outcome Measures:
  • To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n [ Time Frame: Approximately 2 years ]
  • Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Approximately 2 years ]
  • Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Approximately 2 years ]
  • Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Approximately 2 years ]

Enrollment: 40
Study Start Date: June 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage I-Dose Escalation Drug: GDC-0994
Escalating doses of GDC-0994 until maximum tolerated dose is reached
Experimental: Stage II-Cohort-Expansion Drug: GDC-0994
Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • 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 RECIST 1.1
  • Life expectancy >= 12 weeks
  • Adequate hematologic and end organ function
  • Consent to provide archival tissue

Exclusion Criteria:

  • History of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatment
  • History of parathyroid disorder or history or malignancy-associated hypercalcemia requiring therapy in the past 6 months
  • Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
  • History of glaucoma
  • Intraocular pressure > 21 mmHg as measured by tonometry
  • Predisposing factors to retinal vein occlusion, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy
  • History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration
  • Allergy or hypersensitivity to components of the GDC-0994 formulation
  • 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 or 5 times the half-life whichever is longer
  • Current severe, uncontrolled systemic disease
  • History of clinically significant cardiac dysfunction
  • Pregnancy, lactation, or breastfeeding
  • Active autoimmune disease
  • Inability or unwillingness to swallow pills
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
  • 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 warfarin or thrombolytic anticoagulants
  • Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
  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: NCT01875705

Locations
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Tennessee
Nashville, Tennessee, United States, 37203
France
Villejuif, France, 94805
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01875705     History of Changes
Other Study ID Numbers: GO28885  2013-000566-10 
Study First Received: June 10, 2013
Last Updated: November 1, 2016

ClinicalTrials.gov processed this record on February 24, 2017