Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors or Progressive or Recurrent Stage III or Stage IV Non-Small Cell Lung Cancer - Full Text View

Sponsored by:	University of California, Davis
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00408499

Purpose

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	Intervention	Phase
Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific	Biological: cetuximab Drug: erlotinib hydrochloride	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Erlotinib hydrochloride Erlotinib Cetuximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Response rate [ Designated as safety issue: No ]
Objective status as measured by complete, non-complete, and partial response, progressive and stable disease [ Designated as safety issue: No ]
Best response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of molecular markers for biologic effects and predictive response [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	62
Study Start Date:	August 2006
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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)

Secondary

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosed with one of the following:
- Cytologically or histologically confirmed advanced solid tumor meeting the following criteria*:
  - No standard effective therapy exists
  - Ineligible for additional standard effective therapies (e.g., ECOG performance status 2)
  - Evaluable disease (e.g., bone metastases, pleural fluid, ascites) allowed
- Cytologically or histologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria**:
  - Stage IIIB (with pleural effusion) or IV disease
    - Stage IIIA and IIIB disease that has progressed or recurred after standard effective therapy may be allowed
  - Progressive or recurrent disease after treatment with platinum-based therapy
  - Measurable disease as defined by RECIST criteria
    - Disease in previously irradiated sites is considered measurable if there is clear disease progression
Asymptomatic treated (surgical resection or radiotherapy) brain metastasis allowed, if patients are neurologically stable and have been off steroids and anticonvulsants for ≥ the past 4 weeks NOTE: *Phase I

NOTE: **Phase II

PATIENT CHARACTERISTICS:

Life expectancy ≥ 3 months
Zubrod performance status (PS) 0-2 (Phase I)
Zubrod PS 0-1 (Phase II)
Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 45 mL/min
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 2.5 times ULN
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Able to take and retain oral medication
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer from which the patient is currently in complete remission
No active or uncontrolled infection
No significant history of uncontrolled cardiac disease, including, but not limited to, the following:
- Uncontrolled hypertension
- Unstable angina
- Myocardial infarction within the past 6 months
- Uncontrolled congestive heart failure
- Cardiomyopathy with decreased ejection fraction
No prior severe infusion reaction to a monoclonal antibody
No known HIV positivity
No acute hepatitis
Hepatitis C antibody negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Any number of prior chemotherapy regimens allowed (Phase I)
No more than 2 prior treatments for advanced NSCLC (Phase II)
- Patients with recurrent stage III disease may have had up to 2 prior treatments (including primary therapy)
At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C) and recovered
At least 2 weeks since prior radiotherapy and recovered
Prior adjuvant therapy or concurrent chemoradiotherapy allowed (Phase II)
Prior trastuzumab (Herceptin®) allowed
No prior epidermal growth factor receptor-directed therapy
No concurrent chemotherapy, biologic therapy, or targeted therapies
No other concurrent anticancer or investigational therapy
No routine prophylactic use of filgrastim (G-CSF) or sargramostim (GM-CSF)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00408499

Locations

United States, California
University of California Davis Cancer Center	Recruiting
Sacramento, California, United States, 95817
Contact: Corinne Turrell, CCRP 916-734-3089 corinne.turrell@ucdmc.ucdavis.edu

Sponsors and Collaborators

University of California, Davis

Investigators

Study Chair:	David R. Gandara, MD	University of California, Davis
Investigator:	Corinne Turrell, CCRP	University of California, Davis

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of California Davis Cancer Center ( David R. Gandara )
Study ID Numbers:	CDR0000517090, UCDCC-177, BMS-4608, BMS-CA225-261
Study First Received:	December 6, 2006
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00408499 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Erlotinib
Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Cetuximab

Non-small Cell Lung Cancer
Protein Kinase Inhibitors
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Thoracic Neoplasms
Erlotinib
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cetuximab
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 01, 2009