A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0973 in Combination With GDC-0068 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

Neoplasms Clinical Trial

Official title:

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of GDC-0973 and GDC-0068 in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01562275
• Other study ID #: GE28079
• Status: Completed
• Phase: Phase 1
• First received: March 21, 2012
• Last updated: December 1, 2015
• Start date: April 2012
• 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 open-label, multicenter, Phase Ib dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0068 administered in combination in patients with locally advanced or metastatic solid tumors. Cohorts of patients will receive multiple ascending doses of GDC-0973 and GDC-0068. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• 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 therapies either do not exist or have 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

Exclusion Criteria:

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

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

• Anti-cancer therapy within 28 days prior to first dose of study drug, except as stated in protocol

• History of type I or type II diabetes mellitus requiring insulin

• Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease)

• Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B or hepatitis C virus

• Active autoimmune disease

• Pregnant or lactating women

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

• History of glaucoma

• History of retinal vein occlusion

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• GDC-0068
multiple doses
• GDC-0973
multiple doses

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities		approximately 24 months	No
Primary	Nature of dose-limiting toxicities		approximately 24 months	No
Primary	Estimation of the maximum tolerated dose		approximately 24 months	No
Primary	Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Primary	Nature of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Primary	Incidence of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Primary	Nature of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Primary	Severity of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Primary	Severity of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0		approximately 24 months	No
Secondary	Pharmacokinetic parameters of GDC-0973 and GDC-0068: total exposure		Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3	No
Secondary	Pharmacokinetic parameters of GDC-0973 and GDC-0068: maximum plasma concentration		Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3	No
Secondary	Pharmacokinetic parameters of GDC-0973 and GDC-0068: minimum concentration		Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3	No
Secondary	Objective response for patients with measurable disease according to RECIST criteria		approximately 24 months	No
Secondary	Duration of objective response for patients with measurable disease according to RECIST criteria		approximately 24 months	No
Secondary	Progression-free survival for patients with measurable disease according to RECIST criteria		approximately 24 months	No