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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00596648
First received: January 8, 2008
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: XL184
Drug: erlotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of XL184 With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • In Phase 1 of the study, to evaluate pharmacodynamic effects of XL184 administration in combination with erlotinib [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • In Phase 2 of the study, to assess pharmacodynamic effects of XL184 administration either alone or with erlotinib [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: December 2007
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Arm
Escalating doses of XL184 + erlotinib
Drug: XL184
Capsules administered orally daily
Drug: erlotinib
Tablets administered orally daily.
Experimental: Phase 2 Arm 1
XL184 + erlotinib (dose determined from Phase 1 portion of study)
Drug: XL184
Capsules administered orally daily
Drug: erlotinib
Tablets administered orally daily.
Experimental: Phase 2 Arm 2
XL184 administered as a single agent
Drug: XL184
Capsules administered orally daily

  Eligibility

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

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
  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: NCT00596648

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

No publications provided

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00596648     History of Changes
Other Study ID Numbers: XL184-202
Study First Received: January 8, 2008
Last Updated: September 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
Lung Cancer
Non-Small-Cell Lung Cancer
NSCLC

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

ClinicalTrials.gov processed this record on August 21, 2014