An Open-Label, Phase I, Dose-Escalation Study of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable

Genentech, Inc.0 sites60 target enrollmentMarch 2008

ConditionsNon-Hodgkin's Lymphoma, Solid Cancers

InterventionsGDC-0941

DrugsGDC-0941

Overview

Phase: Phase 1
Intervention: GDC-0941
Conditions: Non-Hodgkin's Lymphoma, Solid Cancers
Sponsor: Genentech, Inc.
Enrollment: 60
Primary Endpoint: Occurrence of adverse events by NCI CTCAE grade and associated dose of GDC-0941
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is an open-label, Phase I, dose-escalation study using a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of orally administered GDC-0941 administered QD. This study will include patients with locally advanced or metastatic solid tumors, NHL, or multiple myeloma (MM) (expansion stage only) for which standard therapy either does not exist or has proven ineffective or intolerable.

Registry

clinicaltrials.gov

Start Date

March 2008

End Date

July 2012

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Genentech, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically documented, incurable, locally advanced or metastatic solid malignancy or NHL without leukemic phase that has progressed or has failed to respond to at least one prior regimen
•Multiple myeloma (MM) patients (only in Stage 2): documented pathologic diagnosis of MM that has relapsed or that has failed to respond after treatment with at least one prior systemic therapy (other than corticosteroid monotherapy)
•Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) or per International Working Group (IWG) response criteria for Non-Hodgkin's lymphoma (NHL) patients
•Life expectancy of \>= 12 weeks
•Documented willingness to use an effective means of contraception for both men and women while participating in the study
•For patients participating in Stage 1 after an adequate exposure has been predicted or observed on the basis of PK analysis and for approximately 12 patients participating in Stage 2 (excluding patients with MM): A biopsy-accessible lesion from which tissue can be obtained safely with CT guidance or direct visualization and agreement from the patient to undergo sequential (pre-treatment and post-treatment) biopsies.
•For patients participating in Stage 2 DCE-MRI and MRS imaging: Patients will have at least one metastatic liver lesion measuring \>= 5 cm in one dimension or one tumor lesion elsewhere measuring \>= 2 cm in one dimension (lung and mediastinum lesions do not qualify) on the basis of CT scans

Exclusion Criteria

•Leptomeningeal disease as the only manifestation of the current malignancy
•History of Type 1 or 2 diabetes mellitus requiring regular medication
•Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytics
•Inability or unwillingness to swallow pills
•Malabsorption syndrome or other condition that would interfere with enteral absorption
•Known untreated CNS malignancies or treated brain metastases that are not radiographically stable for \>= 3 months
•Congenital long QT syndrome or QTc \> 500 msec, as determined by at least two of the three baseline ECG measurements
•Active congestive heart failure or ventricular arrhythmia requiring medication
•Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
•Active infection requiring intravenous (IV) antibiotics

Arms & Interventions

1

Intervention: GDC-0941

Outcomes

Primary Outcomes

Occurrence of adverse events by NCI CTCAE grade and associated dose of GDC-0941

Time Frame: Through study completion or early study discontinuation

Occurrence of dose-limiting toxicities (DLTs) by NCI CTCAE grade and associated dose of GDC-0941

Time Frame: Through study completion or early study discontinuation

Occurrence of Grade 3 or 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0941

Time Frame: Through study completion or early study discontinuation

PK parameters after single and multiple doses of GDC-0941

Time Frame: Through study completion or early study discontinuation

Secondary Outcomes

Positron emission tomography (PET) response for patients with detectable FDG tumor uptake at baseline(Through study completion or early study discontinuation)
Best overall 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)