Clinical trial NCT00491816: Erlotinib Plus Chemotherapy for Treatment of Triple Negative Breast Cancer
Official title: Phase II Trial of Neoadjuvant Erlotinib Plus Chemotherapy for Treatment of ER Negative, PgR Negative and HER-2 Negative Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: breast
cancer
breast cancer
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2007-06-26
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Study Objective:

To assess the pathological complete response rate (pCR) with 4-6 cycles of neoadjuvant chemotherapy plus erlotinib in patients with triple negative breast cancer.

Detailed description: Twenty percent of women with breast cancer have triple negative breast cancer. The standard treatment for triple negative breast cancer is typically a combination of chemotherapy, surgery, +/- radiation therapy. When treated with standard therapy women with triple negative breast cancer have a worse long term outcomes as compared to women who do not have triple negative breast cancer. Triple negative breast cancer cells usually have a surface marker called EGFR (epidermal growth factor receptor). Women whose breast cancer cells have the EGFR surface marker have worse long term outcomes as compared to women whose tumors do not have the EGFR marker. Erlotinib (Tarceva) targets EGFR and is currently used for treatment of other cancers like lung and pancreas. This study will assess a combination of chemotherapy with erlotinib in women with triple negative breast cancer.

For breast cancer patients who receive chemotherapy first and then get surgery, long-term survival is longer for women who do not have any microscopic cancer at the time of surgery. The primary objective of this study is to assess whether a combination of chemotherapy and erlotinib will result in no evidence of microscopic disease (pCR) at the time of surgery in greater than 20% of enrolled subjects. After completing all chemotherapy, patients will also receive maintenance erlotinib for 12 months. This is given to study the tolerability of maintenance Erlotinib and also to evaluate if maintenance erlotinib will decrease the rate of tumor recurrence.

Eligibility criteria: Inclusion Criteria:

* Female patient ≥ 18 years of age
* Histologically proven stage II or III adenocarcinoma of the breast
* Patients must be candidates for neoadjuvant treatment (tumor size \> 2 cm, T2, T3, T4 and/or clinical N1 or N2)
* Estrogen Receptor negative, Progesterone Receptor negative and HER-2 negative disease (IHC 0 or 1+ and/or FISH negative)
* Performance status of 2 or better
* No prior chemotherapy or endocrine therapy
* If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months after the last dose of study drug
* Adequate bone marrow function: neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3, and hemoglobin ≥ 11 g/dL
* Adequate kidney function: serum creatinine ≤ 1.5 mg/dl and/or creatinine clearance of ≥ 60 mL/min
* Adequate hepatic function: transaminases \< 2 x upper limit of normal and total bilirubin ≤ 1.5 mg/dL
* Patients must have a serum albumin ≥ 3.0 g/dL
* Patients must have a Prothrombin Time, Partial Thromboplastin Time within normal limits
* Patients must be informed of the investigational nature of the study, and must sign an informed consent in accordance with the institutional rules
* Pretreatment lab values must be performed within 14 days of patient registration, and other baseline studies within 30 days
* Patients will have a baseline mammogram, bone scan, CT chest and abdomen

Exclusion Criteria:

* Patients with metastatic disease are excluded from study
* The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications
* Pregnancy or lactation
* Prior use of an Epidermal growth factor receptor inhibitor
* Patients with a history of chronic pulmonary disease are excluded from study
* Patients with inadequate laboratory values (as defined above) are excluded from study
* Patients with NCI common toxicity criteria (CTC) grade 2 or greater peripheral neuropathy are excluded from study
* Patients with active infection are excluded from study
* Patients with concomitant or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are excluded from study
* Patients with emotional limitations are excluded from study
* Patients with inflammatory breast cancer will be excluded

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: After 18 weeks of neoadjuvant therapy
Secondary outcomes:
measure: Estimation of change in ki-67 (proliferation) after 2 cycles of neoadjuvant carboplatin/docetaxel based chemotherapy
timeFrame: After 2 cycles (6 weeks) of therapy
measure: Estimation of change in ki-67 after 2 cycles of carboplatin/docetaxel based neoadjuvant chemotherapy plus erlotinib
timeFrame: After 2 cycles (6 weeks) of therapy
measure: Assessment of toxicity of the combination of carboplatin/docetaxel chemotherapy plus erlotinib
timeFrame: During neoadjuvant chemotherapy
measure: Assessment of tolerability of 12 months of maintenance erlotinib treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Priyanka Sharma, M.D.
role: PRINCIPAL_INVESTIGATOR
References: