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

NCT01875705 | Completed Phase 1

• 2 other identifiers: GO288852013-000566-10
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 4

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

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (4)

• 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

Study Arms (2)

Stage I-Dose Escalation

EXPERIMENTAL

Drug: GDC-0994

Stage II-Cohort-Expansion

EXPERIMENTAL

Drug: GDC-0994

Interventions

GDC-0994 DRUG

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

Stage I-Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, 06520, United States

Location

Karmanos Can Inst

Detroit, Michigan, 48201, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

MeSH Terms

Interventions

ravoxertinib

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2013
• First Posted: June 12, 2013
• Study Start: June 21, 2013
• Primary Completion: September 23, 2016
• Study Completion: September 23, 2016
• Last Updated: April 6, 2018

Record last verified: 2018-04

Locations

FR (1); US (3)