A Study of XL184 (Cabozantinib) With or Without Erlotinib in Adults With Non-Small Cell Lung Cancer

September 17, 2013 updated by: Exelixis

A Phase 1b/2 Study of XL184 With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer

In Phase 1 of this study, the purpose is to evaluate the safety, tolerability, and highest safe dose of the multiple receptor tyrosine kinase inhibitor (including VEGFR2, MET, and RET) XL184 in combination with the EGFR inhibitor erlotinib administered to adults with Non-Small-Cell Lung Cancer (NSCLC). In Phase 2 of this study, the purpose is to evaluate the objective response rate of daily oral administration of XL184 with or without erlotinib in subjects with NSCLC who have progressed after responding to treatment with erlotinib.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Katmai Oncology Group
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University Medical Center
      • Sacramento, California, United States, 95817
        • University of California, Davis
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University/Lombardi Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Minnesota
      • St. Louis Park, Minnesota, United States, 55416
        • Park Nicollet Institute
    • New Jersey
      • Berkeley Heights, New Jersey, United States, 07922
        • Summit Medical Group
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute
      • Seattle, Washington, United States, 98109
        • University of Washington/ Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 confirmed NSCLC and Stage 3b or 4 NSCLC (Phase 1 only), Stage 3b or 4 NSCLC (Phase 2 only)
  • Documented progressive disease following a prior RECIST response to monotherapy with erlotinib OR documented progressive disease following stable disease of at least 6 months on monotherapy with erlotinib (Phase 2 only)
  • Must have tolerated erlotinib at the maximal dose that will be administered in Phase 2 only (or at a higher dose) for a minimum of 6 weeks
  • Measurable disease per RECIST (Phase 2 only)
  • At least 18 years old
  • ECOG performance status of 0 or 1
  • Adequate organ and marrow function
  • Sexually active subjects must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatment (excluding women who are not of child bearing potential and men who have been sterilized).
  • Female subjects of childbearing potential must have a negative pregnancy test at enrollment
  • No other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed ≥ 2 years previously, and currently with no evidence of disease).
  • Capable of understanding and complying with the protocol, and written informed consent

Exclusion Criteria:

  • Received anti-cancer treatment within 4 weeks, except erlotinib, prior to first dose (Phase 1 only)
  • In Phase 2 only: the subject has received:

    • Small molecule inhibitors of VEGFR2/KDR OR
    • An investigational anti-cancer agent within 4 weeks of the first dose of study drug OR
    • An investigational agent that targets EGF or EGFR at any time OR
    • An approved agent that targets EGF or EGFR (with the exception of erlotinib and gefitinib) at any time unless approved by Exelixis OR
    • Anti-cancer therapy within 4 weeks (with the exception of gefitinib and erlotinib) of the first dose of study drug OR
    • Prior therapy with a c-Met inhibitor
  • Not recovered to NCI CTCAE v.3 Grade ≤1 from clinically significant adverse events due to antineoplastic agents, investigational drugs, or other medications administered prior to study enrollment
  • Symptomatic or uncontrolled brain metastases requiring current treatment, including steroids and anticonvulsants
  • History of significant hematemesis or recent history of hemoptysis
  • Presence of cavitation, central lesion, or lesion abutting a major blood vessel
  • Intercurrent illness such as hypertension or cardiac arrhythmias or recent history of significant disease such as congestive heart failure
  • Pregnant or breastfeeding
  • Active bacterial or viral infection requiring systemic treatment
  • Allergy or hypersensitivity to components of either the XL184 or erlotinib formulations
  • Incapable of understanding and complying with the protocol or unable to provide informed consent
  • History of idiopathic pulmonary fibrosis or interstitial lung disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Arm
Escalating doses of XL184 + erlotinib
Capsules administered orally daily
Tablets administered orally daily.
Experimental: Phase 2 Arm 1
XL184 + erlotinib (dose determined from Phase 1 portion of study)
Capsules administered orally daily
Tablets administered orally daily.
Experimental: Phase 2 Arm 2
XL184 administered as a single agent
Capsules administered orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
In Phase 1 of the study: evaluate safety, tolerability, and maximum tolerated dose of daily oral administration of XL184 in combination with erlotinib to subjects with NSCLC
Time Frame: Assessed at each visit
Assessed at each visit
In Phase 1 of the study, to evaluate pharmacodynamic effects of XL184 administration in combination with erlotinib
Time Frame: Assessed at periodic visits
Assessed at periodic visits
In Phase 1 of the study, to characterize pharmacokinetic parameters of single agent erlotinib, and of XL184 in combination with erlotinib
Time Frame: Assessed at periodic visits (approx. every 8 weeks)
Assessed at periodic visits (approx. every 8 weeks)
In Phase 2 of the study, to estimate the objective response rate of XL184 with or without erlotinib in adults with NSCLC who have progressed after responding to erlotinib
Time Frame: Assessed approx. every 8 weeks
Assessed approx. every 8 weeks
In Phase 2 of the study, to assess pharmacodynamic effects of XL184 administration either alone or with erlotinib
Time Frame: Assessed at periodic visits
Assessed at periodic visits

Secondary Outcome Measures

Outcome Measure
Time Frame
In Phase 1 and 2 of the study, to evaluate the long-term safety and tolerability of XL184 administered either alone or in combination with erlotinib
Time Frame: Assessed at periodic visits
Assessed at periodic visits
In Phase 2 of the study, to assess progression-free survival, duration of response, and overall survival following treatment with XL184 either alone or in combination with erlotinib
Time Frame: Assessed at periodic visits (approx. every 8 weeks)
Assessed at periodic visits (approx. every 8 weeks)
In Phase 2 of the study, to characterize pharmacokinetic parameters of XL184 as a single agent and XL184 in combination with erlotinib in subjects with NSCLC
Time Frame: Assessed at periodic visits (every 8 weeks)
Assessed at periodic visits (every 8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

January 8, 2008

First Submitted That Met QC Criteria

January 8, 2008

First Posted (Estimate)

January 17, 2008

Study Record Updates

Last Update Posted (Estimate)

September 19, 2013

Last Update Submitted That Met QC Criteria

September 17, 2013

Last Verified

September 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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