A Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

Solid Cancers Clinical Trial

Official title:

A Phase Ib, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996892
• Other study ID #: MEK4752g
• Secondary ID: GO01330
• Status: Completed
• Phase: Phase 1
• First received: October 12, 2009
• Last updated: December 1, 2015
• Start date: November 2009
• Est. completion date: January 2015

Study information

• Verified date: December 2015
• 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 Ib dose-escalation study designed to assess the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0941 administered in combination in patients with solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• 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 Response Evaluation Criteria in Solid Tumors (RECIST)

• Life expectancy >= 12 weeks

• Adequate hematologic and end organ function

• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

• History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment

• History of prior significant toxicity from another PI3K pathway inhibitor requiring discontinuation of treatment

• Allergy or hypersensitivity to components of the GDC-0973 or GDC-0941 formulations

• 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 before the first dose of study drug treatment in Cycle 1

• History of diabetes requiring daily medication, or history of Grade >= 3 fasting hyperglycemia

• Current severe, uncontrolled systemic disease

• History of clinically significant cardiac or pulmonary dysfunction

• History of malabsorption or other condition that would interfere with enteral absorption

• 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 anticoagulants, such as warfarin, heparin, or thrombolytics

• Active autoimmune disease

• Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment

• Pregnancy, lactation, or breastfeeding

• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms

• No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays

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-0941
Repeating oral dose
• GDC-0973/XL518
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		Through study completion or early study discontinuation	No
Primary	Incidence, nature and severity of adverse events and serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0		Through study completion or early study discontinuation	No
Primary	PK parameters of GDC-0941 and GDC-0973 (total exposure, maximum plasma\n\nconcentration, and minimum concentration)		Through study completion or early study discontinuation	No
Secondary	Objective response, duration of objective response, and progression-free survival (PFS) for patients with measurable disease according to RECIST		Through study completion or early study discontinuation	No