A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
- Registration Number
- NCT01875705
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Stage I-Dose Escalation GDC-0994 - Stage II-Cohort-Expansion GDC-0994 -
- Primary Outcome Measures
Name Time Method Dose-limiting toxicities Approximately 2 years Pharmacokinetics: Area under the concentration-time curve Approximately 2 years Pharmacokinetics: Time to maximum plasma concentration Approximately 2 years Pharmacokinetics: Apparent terminal elimination half-life Approximately 2 years Safety: Incidence of adverse events Approximately 2 years Maximum tolerated dose Approximately 2 years Pharmacokinetics: Maximum plasma concentrations Approximately 2 years Pharmacokinetics: Minimum plasma concentrations Approximately 2 years
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (4)
Sarah Cannon Research Inst.
🇺🇸Nashville, Tennessee, United States
Institut Gustave Roussy; Departement Oncologie Medicale
🇫🇷Villejuif, France
Karmanos Can Inst
🇺🇸Detroit, Michigan, United States
Yale Cancer Center; Medical Oncology
🇺🇸New Haven, Connecticut, United States