Safety Study of XL147 (SAR245408) in Combination With Erlotinib in Adults With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00692640
First received: June 3, 2008
Last updated: March 22, 2012
Last verified: March 2012
  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 (SAR245408)
Drug: Erlotinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of XL147 (SAR245408) in Combination With Erlotinib in Subjects With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Sanofi:

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 ]

Enrollment: 35
Study Start Date: May 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: XL147 (SAR245408)
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
Other Name: Tarceva®

  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 or for which monotherapy with erlotinib is considered standard therapy.
    • in the Cohort Expansion Phase, the subject has advanced or metastatic NSCLC that is no longer responding to therapies known to prolong survival or to other standard therapies and which:

      1. has been previously or currently treated with erlotinib or gefitinib or
      2. with the agreement of the sponsor, has been previously or is currently treated with other EGFR/VEGFR tyrosine kinase inhibitors
  • The subject has measurable or non-measurable lesions by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria.
  • At least 10 unstained slides of tumor tissue, archival or fresh, or paraffin block or a fresh tumor biopsy are identified and designated for central laboratory analysis.
  • 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 selective PI3K 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 uncontrolled 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00692640

Locations
United States, Tennessee
Investigational Site Number 1214
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00692640     History of Changes
Other Study ID Numbers: TED11434, XL147-002
Study First Received: June 3, 2008
Last Updated: March 22, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Sanofi:
Cancer
Solid Tumors
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014