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Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on 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: NCT00408499
Recruitment Status : Completed
First Posted : December 7, 2006
Results First Posted : May 8, 2017
Last Update Posted : May 8, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, 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. Giving erlotinib together with cetuximab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific Drug: cetuximab Drug: erlotinib Phase 1 Phase 2

Detailed Description:



  • Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in patients with advanced solid tumors. (Phase I)
  • Determine the efficacy of this regimen, in terms of objective tumor response rate, in patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum. (Phase II)


  • Determine the maximum tolerated dose of this regimen in these patients. (Phase I)
  • Determine the efficacy of this regimen, in terms of response rate, in these patients. (Phase I)
  • Determine the progression-free and overall survival of patients treated with this regimen. (Phase II)
  • Determine the frequency and severity of toxicities of this regimen in these patients. (Phase II)
  • Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II)
  • Evaluate EGFR protein expression and protein expression of downstream markers (e.g., pMAPK, pAKT, p27, and Ki-67). (Phase II)
  • Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal cells. (Phase II)
  • Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II)
  • Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood mononuclear cells. (Phase II)
  • Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates with response and/or outcome. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study.

  • Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

  • Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined in phase I.

Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and 3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry, polymorphism analysis, and protein expression assays to assess molecular markers (epidermal growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and predictive response.

After completion of phase I treatment, patients are followed for 30 days or until all toxicities resolve. After completion of phase II treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)
Study Start Date : August 2006
Actual Primary Completion Date : April 2009
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Erlotinib + Cetuximab
Daily erlotinib combined with weekly cetuximab
Drug: cetuximab
Cetuximab will be administered intravenously weekly at the maximum tolerated dose (determined in Phase I portion of the study) on a 28 day cycle. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
Other Name: Erbitux

Drug: erlotinib
Erlotinib will be taken by mouth daily on a 28 day cycle. It is in tablet form. The dose will be determined in Phase I portion of the study. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
Other Name: Tarceva

Primary Outcome Measures :
  1. Number of Patients Experiencing a DLT [ Time Frame: baseline through cycle 1 of treatment ]
    Patients will be followed during cycle 1 for the occurrence of a protocol defined dose limiting toxicity

  2. Number of Patients Correlated With Best Overall Response. [ Time Frame: Every two cycles from first dose to last dose of study drugs ]
    To determine the efficacy, as measured by objective tumor response rate (RICIST criteria), of daily oral erlotinib and weekly intravenous cetuximab in patients with advanced NSCLC. Best overall response per patient will be reported below.

Secondary Outcome Measures :
  1. Patient Outcome [ Time Frame: Patients will be followed until death ]
    In the Phase II portion of the study, patients will be followed for both disease free progression by capturing disease progression date and for over all survival by capturing death date.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

  • For the phase I portion of the study (completed 10/05/08), patients must have cytologically or histologically proven advanced solid tumors for which there is no standard effective therapy available.
  • Any number of prior chemotherapy regimens are allowed for the both the Phase I and Phase II portions
  • For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC. Patients with NSCLC that have progressed or recurred after first-line therapy for stage IIIA or IIIB may also be considered.
  • Patients must have measurable disease by RECIST criteria for the Phase II portion. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy. Patients with evaluable disease (bone metastases, pleural fluid, ascites, etc.) may be included in the phase I portion of the trial (completed 10/08/08).
  • Must be 18 years of age or older.
  • Patients must have a performance status of 0 -2.
  • Patients must have an estimated survival of at least 3 months.
  • Any prior chemotherapy must have been completed at least 4 weeks prior to start of treatment. For prior mitomycin chemotherapy a 6-week interval is required. Prior radiation must have been completed at least 2 weeks prior to start of therapy. Patients must have recovered from acute reversible medically significant side effects of prior chemotherapy regimens or radiotherapy to NCI-CTC < grade 1 (excluding alopecia). Prior herceptin is allowed.
  • Patients must have adequate renal function as documented by a serum creatinine < 1.5 mg/dl or a calculated creatinine clearance of > 45 ml/min (see protocol Appendix D for formula for calculating creatinine clearance).
  • Patients must have adequate liver function as documented by serum bilirubin < 1.5 x ULN. AST must be < 2.5 x institutional upper limit of normal.
  • Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count of >100 000/mm3.
  • Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 2 weeks.
  • All patients must give voluntary written informed consent.
  • Patients must be able to take and retain oral medication.
  • Documentation of a negative serum pregnancy test.
  • Patients on coumadin should have their INR monitored at least once per week or more frequently depending on the investigator's judgment. There have been some case reports of increased INR when coumadin is co-administered with erlotinib.

Exclusion criteria

  • Patients who have received erlotinib, cetuximab, or any other EGFR-directed therapy (excluding herceptin).
  • Patients with symptomatic brain metastasis or still requiring steroids and anti-convulsants may not be included.
  • For the phase II portion of the study, no other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, and any other cancer from which the patient has been disease-free for over five years
  • Patients with acute hepatitis or known HIV.
  • Patients with active or uncontrolled infection.
  • Patients with significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
  • Patients with prior severe infusion reaction to a monoclonal antibody.
  • Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
  • Pregnant or breastfeeding females as the effects of these drugs on the unborn fetus are unknown.

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): NCT00408499

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United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
National Cancer Institute (NCI)
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Study Chair: David R. Gandara, MD University of California, Davis

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Responsible Party: University of California, Davis Identifier: NCT00408499    
Other Study ID Numbers: CDR0000517090
P30CA093373 ( U.S. NIH Grant/Contract )
UCDCC-177 ( Other Identifier: University of California Davis )
BMS-4608 ( Other Identifier: Bristol Myers Squibb )
BMS-CA225-261 ( Other Identifier: Bristol Myers Squibb )
First Posted: December 7, 2006    Key Record Dates
Results First Posted: May 8, 2017
Last Update Posted: May 8, 2017
Last Verified: January 2017
Keywords provided by University of California, Davis:
unspecified adult solid tumor, protocol specific
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action