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

Breast Cancer Clinical Trial

Official title:

A Phase II Study of OSI-774 (Tarceva) and Gemcitabine for Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00059852
• Other study ID #: NCCTG-N0234
• Secondary ID: NCI-2012-02529CD
• Status: Completed
• Phase: Phase 2
• First received: May 6, 2003
• Last updated: December 5, 2016
• Start date: June 2003
• Est. completion date: January 2009

Study information

• Verified date: December 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy such as gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with erlotinib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with erlotinib in treating patients who have metastatic breast cancer that has been previously treated with an anthracycline and/or a taxane.

Description:

OBJECTIVES:

• Determine the anti-tumor activity of erlotinib and gemcitabine in patients with metastatic breast cancer previously treated with anthracycline and/or taxane.

• Determine the adverse event profile of this regimen in these patients.

• 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.

• 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: January 2009
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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/mm^3

• Platelet count at least 100,000/mm^3

• 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

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• erlotinib hydrochloride

• gemcitabine hydrochloride

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Medcenter One Health System	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CentraCare Health Plaza	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 KA, Tenner K, Hillman D, Dueck AC, Hobday TJ, Northfelt DW, Moreno-Aspitia A, Roy V, LaPlant B, Allred JB, Stella PJ, Lingle WL, Perez EA. Cytokeratin-19 and mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437. Clin Cancer Res. 2011 Nov 15;17(22):7183-93. doi: 10.1158/1078-0432.CCR-11-0981. — View Citation

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.

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate		Up to 5 years	No
Secondary	overall survival		Up to 5 years	No