A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 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-0623 Administered Daily in Patients With Locally Advanced or Metastatic Solid Tumors

This is an open-label, multicenter, Phase I dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0623 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) followed by an expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0623 administered orally on a 21 day on/7-day off dosing schedule.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: GDC-0623

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
    • Sacramento, California, United States, 95817
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Tennessee
    • Nashville, Tennessee, United States, 37203

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:

• 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
• Life expectancy >= 12 weeks
• Adequate hematologic and end organ function
• Agreement to use effective form of contraception for the duration of the study
• Consent to provide archival tissue
• For the cohort expansion stage (Stage II): Patients in this cohort must have had no more than four prior systemic therapies for cancer and must have KRAS mutant CRC (Stage II A and B), pancreatic cancer (Stage IIC, or KRAS mutant NSCLC [Stage IID])

Exclusion Criteria:

• History of prior significant toxicity from a MEK pathway inhibitor requiring discontinuation of treatment
• History of parathyroid disorder or history of malignancy-associated hypercalcemia requiring therapy in the last 6 months
• History of retinal vein occlusion (RVO) or predisposing factors to RVO, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy
• Evidence of visible retinal pathology considered a risk factor for retinal vein thrombosis
• History of glaucoma
• Palliative radiotherapy, experimental therapy, or anti-cancer therapy or major surgical procedure within a specified timeframe prior to first dose of study drug
• Current severe, uncontrolled systemic disease
• History of clinically significant cardiac dysfunction
• History of active gastrointestinal bleeding within 6 months prior to screening
• Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, or hepatitis B or C virus
• Active autoimmune disease
• Uncontrolled ascites
• Pregnancy, lactation, or breastfeeding
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• For the Exploratory PK Cohorts (Stage IB and Stage IC): Patients who have a history of or ongoing gastro-esophageal reflux disease or peptic ulcer, or who have gastric pathology or history of gastric surgery which could affect absorption of GDC-0623 from the stomach, will be excluded from these cohorts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0623; Repeating oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of dose-limiting toxicities (DLTs)	Through study completion or early discontinuation
Incidence, nature, and severity of adverse events and serious adverse events, graded according to NCI CTCAE, v4.0	Through study completion or early discontinuation
Pharmacokinetic parameters of GDC-0623 (total exposure, maximum and minimum plasma concentrations, time to maximum plasma concentration, elimination half-life)	Through study completion or early discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response for patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)	Through study completion or early discontinuation
Duration of objective response for patients with measurable disease according to RECIST	Through study completion or early discontinuation
Progression-free survival (PFS) for patients with measurable disease according to RECIST	Through study completion or early discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: April 16, 2010
• First Submitted That Met QC Criteria: April 16, 2010
• First Posted (Estimate): April 20, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: MAP4834g; GO01327 (Other Identifier: Hoffmann-La Roche)