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

NCT ID: NCT00059852

Last Updated: 2016-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2009-01-31

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Keywords

male breast cancer; recurrent breast cancer; stage IV breast cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

gemcitabine + erlotinib

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

Interventions

erlotinib hydrochloride

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edith A. Perez, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Mayo Clinic Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

CCOP - Duluth

Duluth, Minnesota, 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 - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

CCOP - Dayton

Dayton, Ohio, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - Oklahoma

Tulsa, Oklahoma, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Countries

United States

References

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. Epub 2011 Oct 5.

Reference Type: BACKGROUND

PMID: 21976532 (View on PubMed)

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Other Identifiers

NCI-2012-02529

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000298778

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-N0234

Identifier Type: -

Identifier Source: org_study_id