Study of GDC-0973/XL518 in Patients With Solid Tumors - Full Text View

Purpose

This non-randomized, open-label, study will determine the highest safe dose of GDC-0973/XL518, how often it should be taken, how well patients with cancer tolerate GDC-0973/XL518 and will assess the pharmacokinetic effect of midazolam and dextromethorphan on the study drug.

Condition	Intervention	Phase
Solid Tumour	Drug: GDC-0973/XL518 Drug: midazolam Drug: dextromethorphan	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of GDC-0973/XL518 Administered Orally Daily to Subjects With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Dextromethorphan hydrobromide Dextromethorphan Midazolam hydrochloride

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Stage I-II: Safety, tolerability, and maximum tolerated dose of GDC-0973/XL518 [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
Stage III: Maximum plasma concentration of midazolam [ Time Frame: Cycle 1: Days 1 and 15 ] [ Designated as safety issue: No ]
Area under the concentration time curve of midazolam [ Time Frame: Cycle 1: Days 1 and 15 ] [ Designated as safety issue: No ]
Stage III: Maximum plasma concentration of dextromethorphan [ Time Frame: Cycle 1: Days 1 and 15 ] [ Designated as safety issue: No ]
Stage III: Area under the concentration time curve of dextromethorphan [ Time Frame: Cycle 1: Days 1 and 15 ] [ Designated as safety issue: No ]
Stage I-II: Maximum tolerated dose of GDC-0973 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Stage I-II: Plasma pharmacokinetics and pharmacodynamic effects of GDC-0973/XL518 [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
Stage III: Safety: incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment:	120
Study Start Date:	April 2009
Estimated Study Completion Date:	May 2015
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: GDC-0973/XL518 Repeating oral dose Drug: midazolam In Stage III only: single dose of midazolam Drug: dextromethorphan In Stage III only: single dose of dextromethorphan

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival
Disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
Adequate organ and marrow function
Sexually active patients must use medically acceptable methods of contraception during the course of the study and at least 11 days after the last dose of study treatment
Female patients of childbearing potential must have a negative serum pregnancy test at screening
No other history of/or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays

Exclusion Criteria:

Anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study drug
The patient has not recovered to Grade </=1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 28 days prior to study enrollment
The patient has received another investigational agent within 28 days of the first dose of study drug
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
The patient is pregnant or breastfeeding
The patient is known to be positive for the human immunodeficiency virus (HIV)
Allergy or hypersensitivity to components of the GDC-0973/XL518 formulation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00467779

Locations

United States, California

Los Angeles, California, United States, 90095

Stanford, California, United States, 94305-5821
United States, Michigan

Detroit, Michigan, United States, 48201
United States, New York

Buffalo, New York, United States, 14263

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Clinical Trials

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00467779 History of Changes
Other Study ID Numbers:	MEK4592g, GO01329, XL518-001
Study First Received:	April 18, 2007
Last Updated:	May 29, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms
Dextromethorphan
Midazolam
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses

Respiratory System Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on June 18, 2013