Evaluating the Safety and Tolerability of GDC-0349 in Patients With Locally Advanced or Metastatic Solid Tumors or Non Hodgkin's Lymphoma

An Open-Label, Phase I, Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0349 in Patients With Locally Advanced or Metastatic Solid Tumors or Non Hodgkin's Lymphoma

This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetic (PK) of GDC-0349 administered once daily (QD), orally (PO).

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma, Solid Tumor
• Intervention / Treatment: Drug: GDC-0349

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented, locally advanced or metastatic solid malignancy or NHL without leukemic phase that has progressed or failed to respond to at least one prior regimen and/or are not candidates for regimens known to provide clinical benefit
• Evaluable or measurable disease per RECIST v1.1 or IWG response criteria for patients with NHL and/or the following: prostate cancer patients with non-measurable disease are eligible if they have two rising prostate-specific antigen (PSA) levels >= 5 ng/mL measured >= 2 weeks apart that meet the PSA, and Working Group criteria for progression prior to initiation of study treatment, and ovarian cancer patients with non-measurable disease are eligible if they have two rising CA-125 levels greater than the ULN >= 2 weeks apart prior to initiation of study treatment.
• ECOG performance status of 0 or 1 at screening
• Life expectancy of >= 12 weeks
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment
• Documented willingness to use an effective means of contraception for both men and women while participating in the study and for 90 days after the last dose of GDC-0349
• Willingness to provide archival tumor tissue

Exclusion Criteria:

• Leptomeningeal disease as the only manifestation of the current malignancy
• History of Type 1 or 2 diabetes requiring daily medication
• Known untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for >= 3 months prior to initiation of study treatment
• Active congestive heart failure or ventricular arrhythmia requiring medication
• Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to initiation of study treatment
• Active infection requiring intravenous (IV) antibiotics
• Patients requiring any daily supplemental oxygen
• Uncontrolled hypomagnesemia or hypokalemia
• Any condition requiring anti-coagulants such as warfarin, heparin, or anti-thrombotics. Prophylactic anti-coagulation and/or local application of thrombolytic agents for catheter patency may be allowed for patients with normal INR and with prior approval from the Medical Monitor
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus (HIV) infection
• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications
• Significant traumatic injury within 3 weeks prior to initiation of GDC-0349
• Major surgical procedure within 4 weeks prior to initiation of GDC-0349
• Treatment with chemotherapy, hormonal therapy (except GnRH agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, or radiation therapy (except palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment. Kinase inhibitors, approved by national regulatory authorities, may be used up to 2 weeks prior to initiation of GDC-0349, provided that any drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor.
• Palliative radiation to bony metastases within 2 weeks prior to initiation of GDC-0349
• Treatment with an investigational agent within 4 weeks prior to initiation of GDC-0349
• Unresolved toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0349; Oral escalating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and associated dose of GDC-0349	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events by NCI CTCAE v4.0 grade and associated dose of GDC-0349	Up to 2 years
Incidence of Grade 3 and 4 abnormalities in safety related laboratory parameters and associated dose of GDC-0349	Up to 30 days

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 17, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (Estimate): May 19, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: solid cancers
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: MKI4956g; MP00807 (Other Identifier: Hoffmann-La Roche)