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

• Status: Completed
• Trial end date: 2016-09-23
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Ravoxertinib

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