A Study of the Safety and Pharmacokinetics of GDC-0152, Administered Intravenously to Patients With Locally Advanced or Metastatic Malignancies

A Phase Ia, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of GDC-0152, an IAP Protein Antagonist, Administered Intravenously to Patients With Locally Advanced or Metastatic Malignancies

The study consists of two stages. In Stage 1, maximum tolerated dose (MTD) will be determined. In Stage 2, additional patients will be treated at the MTD of GDC-0152.

Study Overview

• Status: Terminated
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: GDC-0152

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

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, incurable, locally advanced or metastatic solid malignancies, or non-Hodgkin's lymphoma (NHL) without leukemic phase
• Disease (either target or non-target lesions) that can be assessed by imaging studies and/or physical examination
• For patients with solid tumors or NHL without leukemic phase, disease progression on or after standard therapy, or a malignancy for which there is no standard therapy
• All prior therapy-related toxicities have recovered to baseline-grade toxicity with the exception of alopecia.
• Life expectancy of ≥ 60 days
• Resting oxygen saturation ≥ 92% on room air
• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria

• History of central nervous system disease
• Chemotherapy, cancer hormonal therapy (except GnRH agonists), radiotherapy, or immunotherapy within 4 weeks prior to Day 1 (6 weeks for nitrosoureas or mitomycin)
• Use of any other investigational agent or device
• Major surgery or significant traumatic injury within 3 weeks prior to Day 1
• Pregnant or nursing
• Clinically significant cardiovascular disease, New York Heart Association (NYHA) Classification Grade 2 or greater congestive heart failure, a ventricular arrhythmia requiring medication within 1 year prior to Day 1, or NYHA Grade 2 or greater peripheral vascular disease on Day 1
• Known HIV infection
• Patients with ongoing inflammatory processes or a Grade ≥ 2 fever or Grade ≥ 2 fever-associated constitutional symptoms (including rigors/chills, sweating, and others determined by the investigator), or a clinically significant systemic infection within the last month
• Any other diseases, 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 or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
• History of any chronic liver disease, active hepatic infection, or evidence of hepatic cirrhosis, or Grade ≥ 2 liver dysfunction.
• Baseline oxygen requirement or history of pulmonary fibrosis
• Any signs or symptoms Grade ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0, at study entry except for alopecia, pain, asymptomatic Grade 2 diffusing capacity of the lung for carbon monoxide (at the discretion of the investigator) or where otherwise specified
• Patients who need to take a concomitant medication, dietary supplement, or food that is a known inhibitor/inducer of the CYP3A4/5 and/or the 2C8 metabolic pathway or that has a narrow therapeutic window and involves these enzymes for their metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• 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-0152; Intravenous escalating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, nature, and severity of adverse events	Through study completion or early study discontinuation
Incidence and nature of dose-limiting toxicities	Through study completion or early study discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters of GDC-0152 (total plasma exposure, maximum plasma concentration, and total plasma clearance)	Through study completion or early study discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Iris Chan, M.D., Ph.D., Genentech, Inc.

Publications and helpful links

General Publications

• Shin YG, Jones SA, Murakami SC, Budha N, Ware J, Wong H, Buonarati MH, Dean B, Hop CE. Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction. Biomed Chromatogr. 2013 Jan;27(1):102-10. doi: 10.1002/bmc.2754. Epub 2012 May 24.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: September 12, 2009
• First Submitted That Met QC Criteria: September 14, 2009
• First Posted (Estimate): September 15, 2009

Study Record Updates

• Last Update Posted (Actual): June 21, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: IAP Antagonist; GDC0152; IAP
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: IAP4050g