Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer

National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP)

Status and phase

Completed

Phase 2

Conditions

Breast Neoplasms

Treatments

Drug: ZD1839 in combination with docetaxel

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00052169

NSABP FB-IR-002

Details and patient eligibility

About

The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.

Full description

Patients with advanced breast cancer continue to have an extremely poor prognosis with an average life expectancy of approximately 2 years. Novel treatments designed to exploit biologic properties of the tumor are urgently required as a means to improve the outcome for the large numbers of patients who relapse after receiving optimal chemotherapy treatments.

Overexpresssion of EGFR and/or TGF-alpha is frequent in human breast cancer and has been correlated in many cases with poor prognostic features. Inhibition of the EGFR pathway has been proposed as a potential therapeutic modality in advanced breast cancer. The antiproliferative activity of ZD 1839 in combination with cytotoxic drugs, such as docetaxel was evaluated in breast cancer cell lines ZR-75-1 and MCF-10A ras that coexpress EGFR and TGF-alpha. Combination treatment demonstrated dose dependent supra-additive growth inhibition and markedly enhanced apoptotic cell death.

Although taxanes bind to the microtubular network in cells that is essential for mitotic and interphase cellular functions, the mechanism by which these agents induce cell death is not entirely clear. Docetaxel has also shown dose-dependent anti-angiogenic activity. Thus, the mechanism(s) of anti-tumor activity of docetaxel remain unclear and combinations of signal transduction pathway inhibition and/or anti-angiogenesis may provide potentiation of concurrent ZD 1839 and docetaxel therapy.

This phase 2 trial is designed to prospectively investigate the efficacy and safetey of combination therapy with ZD 1839 and docetaxel in patients with metastatic breast cancer.

Enrollment

33 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Histologic confirmation of breast cancer
Signed consent
Current diagnosis of metastatic breast cancer
At least one uni-dimensionally measurable lesion with clearly defined margins
Patients taking bisphosphonates for documented prior bone metastasis may be included
Patients may have received prior adjuvant chemotherapy including an anthracycline and/or an alkylating agent. Patients may have received prior paclitaxel or trastuzumab for adjuvant therapy. Patients may not have received prior docetaxel treatment
Patients may have received unlimited prior hormonal therapy regimens for metastatic disease or adjuvant therapy and must have documentation of progressive disease prior to entry. Hormonal therapy must be discontinued at least 2 weeks prior to study entry
Patients may have received prior radiation therapy provided it was completed at least 2 weeks before study entry. Prior radiotherapy to treat bone metastasis or spinal cord compression is permitted provided it was completed prior to study entry
Zubrod performance status 0, 1, or 2
Life expectancy of 12 weeks or more in opinion of investigator
LVEF greater than or equal to LLN without clinical signs or symptoms of heart failure
adequate bone marrow, hepatic, and renal function

Ineligibility Criteria

Prior ZD1839 or other anti EGFR or small molecule TKI
Previous or concurrent chemo or Herceptin for metastatic breast cancer
Unresolved non-permanent major end organ chronic toxicity from previous anticancer therapy greater than CTC grade 2
Radiation therapy less than 14 days before study entry, with exception of RT to treat bone metastasis or spinal cord compression
Incomplete healing of surgical incision from previous major surgery
Newly diagnosed (within 12 weeks) intracerebral metastases
Signs of neurological symptoms consistent with new onset spinal cord compression
Evidence of severe or uncontrolled systemic disease
Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for patient to participate
Pregnancy or breast feeding
Patients who are currently using contact lenses. Patients who discontinue wearing contact lenses prior to study entry are eligible.
Patients with untreated ocular inflammation or infection
Patients with contraindications to corticosteroid use
History of another malignancy within past 5 years that could confound diagnosis or staging of breast cancer
Patients receiving other investigational drugs
Previous docetaxel treatment
Patients currently taking systemic retinoids or herbal medicines
Patients currently taking drugs known to induce Cyt P4503A4