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Safety Study of XL147 in Combination With Erlotinib in Adults With Solid Tumors
This study is currently recruiting participants.
Verified by Exelixis, October 2008
Sponsored by: Exelixis
Information provided by: Exelixis
ClinicalTrials.gov Identifier: NCT00692640
  Purpose

The purpose of this study is to evaluate the safety and tolerability of XL147 in combination with erlotinib (Tarceva®) in subjects with solid tumors. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells. Erlotinib is an orally administered inhibitor of EGFR (also known as HER1) tyrosine kinase. It was approved by the FDA as a single agent for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen and in combination with gemcitabine for first line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.


Condition Intervention Phase
Cancer
Non-Small Cell Lung Cancer
Drug: XL147
Drug: Erlotinib
Phase I

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride Gelatin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title: A Phase 1 Dose-Escalation Study of XL147 in Combination With Erlotinib in Subjects With Solid Tumors

Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Safety, tolerability, and maximum tolerated dose of XL147 administered in combination with erlotinib [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate plasma pharmacokinetics of XL147 and erlotinib when administered in combination [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
  • To evaluate preliminary efficacy of XL147 in combination with erlotinib in adults with refractory solid tumors [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: May 2008
Estimated Study Completion Date: October 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: XL147
Gelatin capsules supplied in 25-mg and 100-mg strengths; daily dosing for 21 days/7 days off
Drug: Erlotinib
Tablets supplied in 25-mg, 100-mg, and 150-mg strengths; daily dosing

  Eligibility

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

Inclusion Criteria:

  • Subjects accrue to one of two phases:

    • in the Dose Escalation Phase, the subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists
    • in the Cohort Expansion Phase, the subject has NSCLC which has previously been treated with erlotinib or gefitinib but no other diagnosis of malignancy or evidence of other malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix) for 2 years prior to screening for this study NOTE: Subjects who are currently on erlotinib and fulfill all inclusion and exclusion criteria may be enrolled to the Cohort Expansion Phase.
  • The subject has measurable or non-measurable lesions by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • The subject has adequate organ and marrow function.
  • The subject has a fasting plasma glucose ≤ 120 mg/dL at screening.
  • The subject is ≥ 18 years old.
  • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  • Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for at least 3 months after the last dose of protocol drug(s).
  • Female subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

  • The subject has previously been treated with a PI3K inhibitor, AKT inhibitor, or mTOR inhibitor.
  • The subject has received:

    • cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic agents (antibodies, immune modulators, cytokines) within 3 weeks or has received nitrosoureas or mitomycin C within 6 weeks before the scheduled first dose of XL147
    • a small-molecule kinase inhibitor (including investigational small molecule kinase inhibitors) excluding small-molecule inhibitors of EGFR or non-cytotoxic hormonal agent within 14 days of the scheduled first dose of XL147
    • other investigational therapy (ie, not specified in exclusion criterion) within 28 days of the first scheduled dose of XL147
  • The subject has not recovered from toxicity due to prior therapy to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or less (except alopecia).
  • The subject has a diagnosis of diabetes mellitus.
  • The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day, heparin, and low-molecular weight heparins are permitted).
  • The subject is taking oral corticosteroids chronically.
  • The subject has prothrombin time/International Normalized Ratio and/or partial thromboplastin time test results at screening that are above 1.3x the laboratory upper limit of normal.
  • The subject has uncontrolled intercurrent illness including but not limited to an active infection or hypertension that would limit compliance with study requirements.
  • The subject has had congestive heart failure, unstable angina, a myocardial infarction, or a stroke within 3 months of entering the study.
  • The subject has a baseline corrected QT interval (QTc) ≥ 460 ms.
  • The subject has psychiatric illness/social situation(s) that would limit compliance with study requirements.
  • The subject is known to be positive for the human immunodeficiency virus.
  • The subject has a previously identified allergy or hypersensitivity to components of the XL147 formulation.
  • The subject is pregnant or breastfeeding.
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00692640

Contacts
Contact: Exelixis Contact Line 1-866-939-4041

Locations
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Erik Troxtel     313-576-8496        
Principal Investigator: Patricia LoRusso, DO            
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Narquita Kizzie     615-329-7426     Narquita.Kizzie@scresearch.net    
Principal Investigator: Howard A. Burris, III, MD            
Sponsors and Collaborators
Exelixis
  More Information

Responsible Party: Exelixis, Inc. ( Christian Scheffold, MD/Director, Clinical Research )
Study ID Numbers: XL147-002
Study First Received: June 3, 2008
Last Updated: October 20, 2008
ClinicalTrials.gov Identifier: NCT00692640  
Health Authority: United States: Food and Drug Administration;   France: Afssaps - French Health Products Safety Agency

Keywords provided by Exelixis:
Cancer
Solid Tumors
NSCLC

Study placed in the following topic categories:
Erlotinib
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009