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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: XL184
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |  | Assessed at each visit | 
| In Phase 1 of the study, to evaluate pharmacodynamic effects of XL184 administration in combination with erlotinib |  | 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 |  | 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 |  | Assessed approx. every 8 weeks | 
| In Phase 2 of the study, to assess pharmacodynamic effects of XL184 administration either alone or with erlotinib |  | Assessed at periodic visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |  | 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 |  | 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 |  | Assessed at periodic visits (every 8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Non-Small-Cell Lung Cancer, NSCLC