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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: GDC-0994; Drug: GDC-0994

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94805
    • Institut Gustave Roussy; Departement Oncologie Medicale
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center; Medical Oncology
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Can Inst
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Inst.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage I-Dose Escalation	Drug: GDC-0994; Escalating doses of GDC-0994 until maximum tolerated dose is reached; Drug: GDC-0994; Recommended dose determined in Stage I-Dose Escalation phase, until disease progression
Experimental: Stage II-Cohort-Expansion	Drug: GDC-0994; Escalating doses of GDC-0994 until maximum tolerated dose is reached; Drug: GDC-0994; Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	Approximately 2 years
Maximum tolerated dose	Approximately 2 years
Dose-limiting toxicities	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
Pharmacokinetics: Apparent terminal elimination half-life	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2013
• Primary Completion (Actual): September 23, 2016
• Study Completion (Actual): September 23, 2016

Study Registration Dates

• First Submitted: June 10, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimate): June 12, 2013

Study Record Updates

• Last Update Posted (Actual): April 6, 2018
• Last Update Submitted That Met QC Criteria: April 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ravoxertinib
• Other Study ID Numbers: GO28885; 2013-000566-10 (EudraCT Number)