Erlotinib Hydrochloride With or Without Cixutumumab in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00778167
Recruitment Status : Completed
First Posted : October 23, 2008
Results First Posted : April 23, 2013
Last Update Posted : May 21, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase I/II trial is studying the side effects and best dose of cixutumumab and to see how well erlotinib hydrochloride works when given together with or without cixutumumab in treating patients with stage III or stage IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether erlotinib hydrochloride is more effective when given together with or without cixutumumab in treating non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Recurrent Non-small Cell Lung Cancer Stage IIIA Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Biological: cixutumumab Drug: erlotinib hydrochloride Other: laboratory biomarker analysis Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/Randomized Phase II Study of the Anti-IGF-1R Monoclonal Antibody IMC-A12 in Combination With Erlotinib Compared With Erlotinib Alone in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Start Date : October 2008
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm I (Enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO once daily on days 1-21. Patients with documented disease progression may cross over and receive treatment on arm II.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Other: laboratory biomarker analysis
Correlative studies

Experimental: Arm II (Enzyme inhibitor and monoclonal antibody therapy)
Patients receive erlotinib hydrochloride PO as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15.
Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Safety and Tolerability of IMC-A12 in Combination With Erlotinib Hydrochloride as Graded by Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0 (DLTs During Cycle One) [ Time Frame: From time of first dose up to 28 days ]
    Patients were evaluable for cohort dose escalation/de-escalation decision making either if they experienced DLTs in cycle 1 or if they had completed 24 of the planned 28 days (85%) dosing of erlotinib and three of the four planned days of weekly dosing of cixutumumab (75%) in cycle 1 in cohorts 1 and 2 in the absence of DLTs. In cohort 3, patients were evaluable for tolerability if they had completed 18 days (85%) dosing of erlotinib and had received the planned day 1 dose of cixutumumab.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

    • Stage IIIA, IIIB, or IV disease
    • Mixed histology permitted provided small-cell elements are not present
  • Measurable disease, defined as ≥ 1unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • Must have failed ≥ 1 platinum-containing chemotherapy regimen
  • CNS metastases are eligible if received prior radiotherapy to site(s) of CNS metastatic disease, or have had definitive resection of CNS metastatic disease and have no overt evidence of neurological deficits, are not requiring anti-epileptics, remain asymptomatic, and have been off steroids for ≥ 8 weeks
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • Leukocytes ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100,000/mm³
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • Fasting serum glucose < 120 mg/dL OR normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-IGF-1R recombinant monoclonal antibody IMC-A122 or erlotinib hydrochloride
  • No poorly controlled diabetes mellitus

    • Patients with a history of diabetes mellitus are eligible, provided their blood glucose is within normal range at screening and they are on a stable dietary or therapeutic regimen for this condition
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • No inability to take oral medications or, in the investigator's opinion, gastrointestinal conditions or abnormalities likely to influence the absorption of oral medications
  • No prior or concurrent exposure to other EGFR or IGFR inhibitors
  • Recovered from all prior therapy with acute effects resolved to ≤ grade 1
  • At least 28 days since prior anticancer or investigational agent (within predicted 5 half-lives of agent)
  • More than 4 weeks since prior radiotherapy to target lesions and documented disease progression at these sites
  • More than 2 weeks since prior radiotherapy to non-target lesions
  • More than 4 months since prior major surgery or hormonal therapy (other than replacement)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00778167

United States, Colorado
University of Colorado
Denver, Colorado, United States, 80217-3364
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: David Camidge University of Colorado, Denver

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00778167     History of Changes
Other Study ID Numbers: NCI-2009-00286
NCI-2009-00286 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COMIRB 08-0044 ( Other Identifier: University of Colorado at Denver )
8148 ( Other Identifier: CTEP )
P30CA046934 ( U.S. NIH Grant/Contract )
N01CM62209 ( U.S. NIH Grant/Contract )
R21CA135595 ( U.S. NIH Grant/Contract )
First Posted: October 23, 2008    Key Record Dates
Results First Posted: April 23, 2013
Last Update Posted: May 21, 2014
Last Verified: March 2013

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antibodies, Monoclonal
Erlotinib Hydrochloride
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action