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

NCT ID: NCT01875705

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-21
• Study Completion Date: 2016-09-23

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.

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Stage I-Dose Escalation

Group Type: EXPERIMENTAL

GDC-0994

Intervention Type: DRUG

Escalating doses of GDC-0994 until maximum tolerated dose is reached

Stage II-Cohort-Expansion

Group Type: EXPERIMENTAL

GDC-0994

Intervention Type: DRUG

Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

Interventions

GDC-0994

Escalating doses of GDC-0994 until maximum tolerated dose is reached

Intervention Type: DRUG

GDC-0994

Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

Intervention Type: DRUG

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, United States

Karmanos Can Inst

Detroit, Michigan, United States

Sarah Cannon Research Inst.

Nashville, Tennessee, United States

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Countries

United States; France

Other Identifiers

2013-000566-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28885

Identifier Type: -

Identifier Source: org_study_id