A Study of 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

NCT00876122 | Completed Phase 1

• 2 other identifiers: GDC4254gGO01299
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Hodgkin's Lymphoma, Solid Cancers

Keywords

NHL; Metastatic Solid Tumors; PI3K Inhibitors; PI3K

Outcome Measures

Primary Outcomes (4)

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

  Through study completion or early study discontinuation

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

  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

  Through study completion or early study discontinuation

• PK parameters after single and multiple doses of GDC-0941

  Through study completion or early study discontinuation

Secondary Outcomes (2)

• 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

Study Arms (1)

1

EXPERIMENTAL

Drug: GDC-0941

Interventions

GDC-0941 DRUG

Escalating oral dose

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Patients requiring any daily supplemental oxygen
• DLco, 50% predicted value corrected for AV and Hgb prior to initiation of study treatment
• Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit of normal (LLN) or hypercalcemia above the ULN for the institution despite adequate electrolyte supplementation or management
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Unknown Facility

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Gallia Levy, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: April 6, 2009
• Study Start: March 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: July 1, 2012
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

GB (1)