Solid Tumor
Conditions
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.
Interventions
DRUGGDC-0994
Escalating doses of GDC-0994 until maximum tolerated dose is reached
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Apparent terminal elimination half-life | Approximately 2 years |
| Pharmacokinetics: Area under the concentration-time curve | Approximately 2 years |
| Pharmacokinetics: Maximum plasma concentrations | Approximately 2 years |
| Pharmacokinetics: Minimum plasma concentrations | Approximately 2 years |
| Pharmacokinetics: Time to maximum plasma concentration | Approximately 2 years |
| Safety: Incidence of adverse events | Approximately 2 years |
| Maximum tolerated dose | Approximately 2 years |
| Dose-limiting toxicities | Approximately 2 years |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
France, United States
Outcome results
None listed