Erlotinib Plus Docetaxel in Treating Patients With Stage IV or Recurrent Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have stage IV or recurrent breast cancer.

Detailed Description
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OBJECTIVES: Determine the antitumor effects of erlotinib and docetaxel, in terms of objective response, stabilization of disease, and progression-free survival, in patients with stage IV or recurrent breast cancer. Determine time to tumor progression in patients treated with this regimen. Compare time to tumor progression in patients who achieve disease stabilization or response after treatment with this regimen and continue to receive erlotinib versus patients who do not receive additional erlotinib. OUTLINE: Patients receive docetaxel IV over 1 hour once weekly for 3 weeks and oral erlotinib once daily beginning on day 1. Treatment repeats every 4 weeks for a minimum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients achieving maximal tumor response or stabilization of disease after 6 courses may continue to receive erlotinib alone until disease progression. Patients are followed for survival. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12-14 months.

Official Title
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A Phase II Study Of The Weekly Administration Of Docetaxel In Combination With The Epidermal Growth Factor Receptor Inhibitor OSI-774 In Recurrent And/Or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV or recurrent adenocarcinoma of the breast Measurable disease Disease recurrence must not be within 1 year of receiving prior adjuvant docetaxel Stable brain metastases allowed Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Male or female Menopausal status Not specified Performance status ECOG (Eastern Cooperative Oncology Group) 0-2 OR Karnofsky 60-100% Life expectancy More than 6 months Hematopoietic WBC(White Blood Count) at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Hemoglobin at least 8 g/dL Hepatic Bilirubin normal AST(aspartate aminotransferase)/ALT(alanine aminotransferase) no greater than 2.5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance at least 60 mL/min No clinically significant proteinuria No significant impairment of renal function Cardiovascular No New York Heart Association class III or IV heart disease No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No inadequately controlled hypertension Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No prior severe hypersensitivity reaction to docetaxel or drugs formulated with polysorbate 80 No other malignancy within the past 10 years except inactive nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, or bilateral breast cancer No ongoing or active infection No peripheral neuropathy greater than grade 1 No other concurrent uncontrolled medical condition that would preclude study participation No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Prior trastuzumab (Herceptin) allowed Chemotherapy See Disease Characteristics No prior chemotherapy for recurrent or metastatic disease Prior adjuvant chemotherapy allowed Endocrine therapy Prior hormonal therapy allowed Radiotherapy Not specified Surgery Not specified Other No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib Plus Docetaxel<br> | Drug: docetaxel<br>* Docetaxel IV infusion weekly for 3 weeks with a one-week break. One cycle is 4 weeks (28 days). Patients' actual weight will be used to calculate dose.<br>* Other names: NSC #628503;Drug: erlotinib hydrochloride<br>* OSI-774 will be taken 1 hour before or 2 hours after meals. Cycle 1 will be administered at dose level -1.If no grade 3 or 4 toxicity occurs during cycle 1, then the patient may proceed to be treated at dose level 0 for the remaining chemotherapy cycles.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 | Response and progression will be evaluated in this study using the criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive Disease: At least a 20% increase in the sum of the LD of target lesions. Stable Disease: Neither sufficient shrinkage nor sufficient increase. | after 6 course (6 months) of combination therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) | Progression free survival was defined as time from the start of treatment to the date of cancer progression, or death, and censored at the date of last follow-up for those without disease progression and still alive. Stable disease is measured from the start of the treatment until progression, taking as reference the smallest measurements recorded since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | 3 years | 
| Overall Survival as of 2008 | Overall survival (OS) was defined as time from the start of treatment to death, and censored at the time of last assessment for survivors. | 5 yrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, male breast cancer