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Carcinoma, Non-Small-Cell LungPhase 1/2NCT00596648

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

A Phase 1/2 study testing XL184 and erlotinib in people with Carcinoma, Non-Small-Cell Lung, run by Exelixis at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
XL184 and erlotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
13 sitesUnited States
Study dates
12 Feb 2008to 2 Aug 2012
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • 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
  • Subjects had to have 15 unstained consecutive slides of archival or fresh tumor tissue (from one tumor block, frozen tumor tissue, or a paraffin block) identified and designated for shipment to the sponsor if permitted by local regulations (including IRB [Institutional Review Board] policies). The eligibility of subjects with < 15 unstained slides of available archival tissue was discussed with the sponsor
  • The subject was at least 18 years old
  • The subject had an ECOG performance status of < 1
  • 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, ALT and 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)

Who cannot join

  • 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
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  • 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
  • The subject had received: Small molecule inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2)/ kinase insert domain receptor (KDR) at anytime, OR; An investigational anti-cancer agent within 4 weeks of the first dose of study drug, OR; Investigational small molecule inhibitors of EGFR at any time, OR; A small molecule inhibitor of epidermal growth factor (EGF)/EGFR at any time (with the exception of erlotinib and gefitinib), OR; Anti-cancer therapy, including radiation therapy, within 4 weeks of the first dose of study drug (with the exception of gefitinib and erlotinib), OR; Prior therapy with a c-Met inhibitor. Recent (within 3 months) radiation therapy to the thoracic cavity including brachytherapy, unless radiation therapy targeted only bone metastasis
  • The subject had not recovered to NCI CTCAE v3.0 Grade ≤1 from clinically significant 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 experienced clinically significant hematemesis or hemoptysis of > 0.5 teaspoon of red blood within 3 months before the first dose of study treatment, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
  • The subject had cavitating pulmonary lesion(s), known endobronchial disease or a pulmonary lesion abutting or encasing a major blood vessel
  • The subject had serious intercurrent illness, such as uncontrolled hypertension (sustained 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 the past 3 months, myocardial infarction, stroke, or transient ischemic attack within the past 6 months
  • The subject was pregnant or breastfeeding
  • The subject had a clinically significant 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
  • The subject had a history of idiopathic pulmonary fibrosis or interstitial lung disease (ILD)

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Summit Medical Group

    Berkeley Heights, New Jersey, 07922

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Yale University School of Medicine

    New Haven, Connecticut, 06520

  • Stanford University Medical Center

    Palo Alto, California, 94305

  • University of California, Davis

    Sacramento, California, 95817

  • Park Nicollet Institute

    Saint Louis Park, Minnesota, 55416

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • University of Washington/ Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Georgetown University/Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

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.

Being tested
XL184, erlotinib
Keywords
Lung Cancer, Non-Small-Cell Lung Cancer, NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XL184Drug

    Capsules administered orally daily

  • erlotinibDrug

    Tablets administered orally daily.

Study groups in NCT00596648
Study groupRoleWhat they receive
Phase 1 ArmExperimentalEscalating doses of XL184 + erlotinib
Receives: Drug: XL184; Drug: erlotinib
Phase 2 Arm 1ExperimentalXL184 + erlotinib (dose determined from Phase 1 portion of study)
Receives: Drug: XL184; Drug: erlotinib
Phase 2 Arm 2ExperimentalXL184 administered as a single agent
Receives: Drug: XL184

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From initial dose up to 160 weeks

  2. 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.

    Measured: From initial dose up to 72 weeks

Secondary outcomes (2)

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

    DOR was defined as the time interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.

    Measured: From initial dose up to 72 weeks

  2. Phase 2: Progression-Free Survival (PFS)

    Progression-free survival is defined as the time from first dose of cabozantinib to disease progression per protocol-defined criteria or death due to any cause, whichever occurs first.

    Measured: From initial dose up to 72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2008 (estimated)
  2. Study start12 Feb 2008
  3. Primary completion2 Aug 2012
  4. Study completion2 Aug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00596648
Sponsor's protocol ID
XL184-202
Status last verified
Dec 2025
First submitted
8 Jan 2008
Last updated
13 Jan 2026
Individual data sharing
No

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