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

NCT00596648 | Completed Phase 1 Results

• 1 other identifier: XL184-202
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 13

Brief Summary

The study consisted of a Phase 1 dose escalation/dose de-escalation portion to determine a safe and tolerable combination dose(s) of cabozantinib and erlotinib, and a Phase 2 Simon optimal 2-stage design portion with randomized assignment of subjects in an equal ratio to determine the objective response rate (ORR) of cabozantinib with or without erlotinib in subjects with non-small cell lung cancer (NSCLC) who have progressed after responding to treatment with erlotinib. The doses of cabozantinib used in this study were based on the salt weight, not the freebase weight.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Lung Cancer; Non-Small-Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (2)

• Phase 1: Duration of Exposure of Cabozantinib With Erlotinib

  Treatment duration was defined as the number of days from the first dose to the last dose (measured in weeks), including any days of treatment interruption that occurred before the last dose of study drug.

  From initial dose up to 160 weeks

• Phase 2: Objective Response Rate (ORR)

  Objective Response Rate is defined as the number of participants for whom the best overall response is complete (CR) or partial response (PR) confirmed by repeat assessments no less than four weeks after the criteria for the initial response were first met.

  From initial dose up to 72 weeks

Secondary Outcomes (2)

• Phase 2: Duration of Response (DOR) in Participants With a CR or PR

  From initial dose up to 72 weeks

• Phase 2: Progression-Free Survival (PFS)

  From initial dose up to 72 weeks

Study Arms (3)

Phase 1 Arm

EXPERIMENTAL

Escalating doses of XL184 + erlotinib

Drug: XL184; Drug: erlotinib

Phase 2 Arm 1

EXPERIMENTAL

XL184 + erlotinib (dose determined from Phase 1 portion of study)

Drug: XL184; Drug: erlotinib

Phase 2 Arm 2

EXPERIMENTAL

XL184 administered as a single agent

Drug: XL184

Interventions

XL184 DRUG

Capsules administered orally daily

Phase 1 Arm; Phase 2 Arm 1; Phase 2 Arm 2

erlotinib DRUG

Tablets administered orally daily.

Phase 1 Arm; Phase 2 Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• Subjects had failed treatment with erlotinib at 150 mg qd
• Subjects had tolerated erlotinib at the dose of the cohort in which they were enrolled (or at a higher dose) for at least 6 weeks (or for the duration of treatment if disease progression had occurred during treatment with erlotinib for less than 6 weeks)
• The subject was at least 18 years old
• The subject had an ECOG performance status of \< 2
• The subject had organ and marrow function as follows: - absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, bilirubin ≤ 1.5 times the upper limit of normal, serum creatinine ≤ 1.5 mg/dL or if serum creatinine \> 1.5 mg/dL calculated creatinine clearance ≥ 60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal, amylase and lipase \< 1.5 times the upper limit of normal
• Sexually active subjects had to agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized)
• Female subjects of childbearing potential had to have a negative pregnancy test at enrollment. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, antiestrogens, or ovarian suppression
• The subject had no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed ≥ 2 years previously, and currently with no evidence of disease)

You may not qualify if:

• The subject had received anti-cancer treatment (eg, chemotherapy, radiotherapy, cytokines, or hormones) within 4 weeks with exception of erlotinib (6 weeks for nitrosoureas or mitomycin C) before the first dose of study drug
• The subject had not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 from clinically significant adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study enrollment
• The subject had symptomatic or uncontrolled brain metastases requiring current treatment, including steroids and anticonvulsants
• The subject had a history of clinically significant hematemesis or a recent history of hemoptysis of \> 0.5 teaspoon of red blood or other signs indicative of pulmonary hemorrhage
• The subject had the presence of cavitation, endobronchial lesion or a lesion abutting a major blood vessel
• The subject had serious intercurrent illness, such as uncontrolled hypertension (sustained blood pressure \[BP\] readings of \> 140 mmHg systolic or \> 90 mmHg diastolic not controlled with anti-hypertensive medication), unhealed wounds from recent surgery or clinically significant cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within 3 months or myocardial infarction within 6 months before the first dose of study drug
• The subject was pregnant or breastfeeding
• The subject had an active infection requiring systemic treatment
• The subject had an allergy or hypersensitivity to components of either the cabozantinib or erlotinib formulations
• The subject was incapable of understanding and complying with the protocol or unable to provide informed consent
• Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• Subjects had: Documented radiological PD, following a prior response, per investigator assessment, to monotherapy with erlotinib, OR; Documented radiological PD, per investigator assessment, following stable disease of at least 6 months on monotherapy with erlotinib
• Subjects who had received subsequent anti-cancer therapy after having progressed on erlotinib (as defined above) also had to have documented radiological PD per investigator assessment to their most recent anti-cancer therapy. If the most recent anti-cancer therapy was erlotinib after having previously progressed on erlotinib (as defined above) the subject also had to have documented radiological PD per investigator assessment to their most recent course of erlotinib
• Subjects had to have tolerated erlotinib at the maximal dose that would be administered in Phase 2 (or at a higher dose) for a minimum of 6 weeks
• Subjects had measurable disease per RECIST

Sponsors & Collaborators

• Exelixis: lead

Study Sites (13)

Katmai Oncology Group

Anchorage, Alaska, 99508, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Georgetown University/Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Park Nicollet Institute

Saint Louis Park, Minnesota, 55416, United States

Location

Summit Medical Group

Berkeley Heights, New Jersey, 07922, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington/ Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Study Officials

• Medical Director

  Exelixis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 17, 2008
• Study Start: February 12, 2008
• Primary Completion: August 2, 2012
• Study Completion: August 2, 2012
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)