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

Solid Cancers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01106599
• Other study ID #: MAP4834g
• Secondary ID: GO01327
• Status: Completed
• Phase: Phase 1
• First received: April 16, 2010
• Last updated: November 1, 2016
• Start date: April 2010
• Est. completion date: August 2014

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Cancers

Intervention

Drug:
• GDC-0623
Repeating oral dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and nature of dose-limiting toxicities (DLTs)		Through study completion or early discontinuation	No
Primary	Incidence, nature, and severity of adverse events and serious adverse events, graded according to NCI CTCAE, v4.0		Through study completion or early discontinuation	No
Primary	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	No
Secondary	Objective response for patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)		Through study completion or early discontinuation	No
Secondary	Duration of objective response for patients with measurable disease according to RECIST		Through study completion or early discontinuation	No
Secondary	Progression-free survival (PFS) for patients with measurable disease according to RECIST		Through study completion or early discontinuation	No