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

Solid Tumour Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00467779
• Other study ID #: MEK4592g
• Secondary ID: GO01329XL518-001
• Status: Active, not recruiting
• Phase: Phase 1
• First received: April 18, 2007
• Last updated: May 5, 2014
• Start date: April 2009
• Est. completion date: May 2015

Study information

• Verified date: May 2014
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumour

Intervention

Drug:
• midazolam
In Stage III only: single dose of midazolam
• dextromethorphan
In Stage III only: single dose of dextromethorphan
• GDC-0973/XL518
Repeating oral dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage I-II: Safety, tolerability, and maximum tolerated dose of GDC-0973/XL518		Through study completion or early study discontinuation	No
Primary	Area under the concentration time curve of midazolam		Cycle 1: Days 1 and 15	No
Primary	Stage III: Maximum plasma concentration of dextromethorphan		Cycle 1: Days 1 and 15	No
Primary	Stage III: Area under the concentration time curve of dextromethorphan		Cycle 1: Days 1 and 15	No
Primary	Stage I-II: Maximum tolerated dose of GDC-0973		2 years	No
Primary	Stage III: Maximum plasma concentration of midazolam		Cycle 1: Days 1 and 15	No
Secondary	Stage I-II: Plasma pharmacokinetics and pharmacodynamic effects of GDC-0973/XL518		Through study completion or early study discontinuation	No
Secondary	Stage III: Safety: incidence of adverse events		1 year	No