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
Overview
- Phase
- Phase 1
- Intervention
- GDC-0994
- Conditions
- Solid Tumor
- Sponsor
- Genentech, Inc.
- Enrollment
- 40
- Locations
- 4
- Primary Endpoint
- Safety: Incidence of adverse events
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility 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
Arms & Interventions
Stage I-Dose Escalation
Intervention: GDC-0994
Stage II-Cohort-Expansion
Intervention: GDC-0994
Outcomes
Primary Outcomes
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: Time to maximum plasma concentration
Time Frame: Approximately 2 years
Pharmacokinetics: Apparent terminal elimination half-life
Time Frame: Approximately 2 years
Pharmacokinetics: Maximum plasma concentrations
Time Frame: Approximately 2 years
Pharmacokinetics: Minimum plasma concentrations
Time Frame: Approximately 2 years
Secondary Outcomes
- To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n(Approximately 2 years)
- Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)
- Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)
- Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(Approximately 2 years)