Clinical trial NCT00596648: A Study of XL184 (Cabozantinib) With or Without Erlotinib in Adults With Non-Small Cell Lung Cancer
Official title: A Phase 1b/2 Study of XL184 With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Lung Cancer
Non-Small-Cell Lung Cancer
NSCLC
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2008-01-17
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Assessed at each visit
measure: In Phase 1 of the study, to evaluate pharmacodynamic effects of XL184 administration in combination with erlotinib
timeFrame: Assessed at periodic visits
measure: In Phase 1 of the study, to characterize pharmacokinetic parameters of single agent erlotinib, and of XL184 in combination with erlotinib
timeFrame: Assessed at periodic visits (approx. every 8 weeks)
measure: 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
timeFrame: Assessed approx. every 8 weeks
measure: In Phase 2 of the study, to assess pharmacodynamic effects of XL184 administration either alone or with erlotinib
timeFrame: Assessed at periodic visits
Secondary outcomes:
measure: 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
timeFrame: Assessed at periodic visits
measure: 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
timeFrame: Assessed at periodic visits (approx. every 8 weeks)
measure: 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
timeFrame: Assessed at periodic visits (every 8 weeks)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University/Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: St. Louis Park
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: Berkeley Heights
country: United States
facility: Summit Medical Group
state: New Jersey
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington/ Seattle Cancer Care Alliance
state: Washington
Study officials:
References: