Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Erlotinib and Gemcitabine in Treating Patients With Metastatic Breast Cancer Previously Treated With An Anthracycline and/or a Taxane

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NCCTG-N0234 N0234, NCT00059852

Objectives

1. Determine the anti-tumor activity of erlotinib and gemcitabine in patients with metastatic breast cancer previously treated with anthracycline and/or taxane.
2. Determine the adverse event profile of this regimen in these patients.
3. Determine whether epidermal growth factor receptor and HER-2 receptor intensity and serum concentrations have an impact on clinical response in patients treated with this regimen.
4. Determine the impact of genetic differences in proteins involved in drug response (transport, metabolism, and mechanism of action) on clinical response and adverse events associated with gemcitabine in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed breast cancer
  • Clinical evidence of metastatic disease



• Candidate for first- or second-line chemotherapy for metastatic disease



• Must have received prior anthracycline or taxane therapy (may have had both in the neoadjuvant, adjuvant, or metastatic setting)



• At least 1 measurable lesion at least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan
  • The following are not considered measurable disease:
    • Small lesions less than 20 mm by CT scan or MRI
    • Bone lesions
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions



• No active CNS metastases (treated CNS metastases stable for more than 8 weeks are allowed)



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• At least 2 weeks since prior immunotherapy
• No prior cetuximab

Chemotherapy

• At least 2 weeks since prior chemotherapy and recovered
• No more than 1 prior chemotherapy regimen for metastatic disease
• No more than 2 prior chemotherapy regimens total, including adjuvant therapy

Endocrine therapy

• Prior hormonal therapy allowed in metastatic and/or adjuvant setting

Radiotherapy

• At least 2 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow
• No prior strontium chloride Sr 89

Surgery

• More than 4 weeks since prior major surgery
• No prior surgical procedures affecting absorption

Other

• No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib or EKB-569)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent antitumor therapy

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 8.5 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN
• Alkaline phosphatase no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No inability to take oral or nasogastric medication
• No requirement for IV alimentation
• No active peptic ulcer disease

Ophthalmic

• No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital abnormality (e.g., Fuch's dystrophy)
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
  • Sub-dermal implants and condoms are not considered acceptable forms of contraception
• No other invasive non-breast malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness

Expected Enrollment

A total of 5-56 patients will be accrued for this study within 20 months.

Outline

This is a multicenter study.

Patients receive gemcitabine IV on days 1 and 8 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response are followed every 6 weeks for up to 5 years or until disease progression (PD). Patients discontinuing study therapy for any other reason are followed every 3 months until PD and then every 6 months for up to 5 years.

Thome S, Hobday T, Hillman D, et al.: Translational correlates, including outcome for patients with ER-/PR-/HER2- (triple negative (TNeg)) disease from N0234, a phase II trial of gemcitabine and erlotinib for pts with previously treated metastatic breast cancer (MBC). [Abstract] J Clin Oncol 25 (Suppl 18): A-1071, 2007.

Graham DL, Hillman DW, Hobday TJ, et al.: N0234: phase II study of erlotinib (OSI-774) plus gemcitabine as first-or second-line therapy for metastatic breast cancer (MBC). [Abstract] J Clin Oncol 23 (Suppl 16): A-644, 39s, 2005.

Pockaj BA, Mukherjee P, Tinder TL, et al.: NCCTG N0338: effect of docetaxel and carboplatin on VEGF, PGE2, and immune cells in patients with stage II or III breast cancer. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-5110, 2008.

Reinholz MM, Kitzmann KK, Hillman D, et al.: Differential gene expression in circulating tumor cells between primary and metastatic breast cancer patients. [Abstract] Breast Cancer Res Treat 106 (1): A-5022, S213-4, 2007.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 507-284-1159 Email: perez.edith@mayo.edu
Stephan Thome, MD, Protocol co-chair		Ph: 402-393-3110

Registry Information
Official Title		A Phase II Study of OSI-774 (Tarceva) and Gemcitabine for Patients with Metastatic Breast Cancer
Trial Start Date		2003-06-02
Trial Completion Date		2009-01-27
Registered in ClinicalTrials.gov		NCT00059852
Date Submitted to PDQ		2003-03-06
Information Last Verified		2004-09-08
NCI Grant/Contract Number		U10-CA25224

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