Open, Single-Arm Phase II Study Assessing Efficacy of ZARNESTRA™ Combined With Tamoxifen in Patients With Advanced or Metastatic Breast Cancer Expressing the Estrogen and/or Progesterone Receptor
- Histologically proven, metastatic or locally advanced inoperable breast cancer
- Tumor considered potentially hormone-sensitive, i.e. presence by IHC of hormone
receptors for estrogens (ER+ for more than 10% of cells) and/or progesterone (Pg+ for
more than 10% of cells) or both. This expression may have been detected on the
primary tumor or at a metastatic site. The method used will be reassessed by IHC if
it involves a radioligand technique whenever it is possible to obtain histological
- Progressing on treatment with tamoxifen, given either as adjuvant treatment or for
advanced/metastatic breast cancer. Any previous treatment with a steroidal or
nonsteroidal antiaromatase in a neo-adjuvant, adjuvant or metastatic situation is
permitted. Likewise, any previous treatment with chemotherapy and/or herceptin in a
nonmetastatic situation is permitted.
- Post-menopausal patients
- Age > 18 years
- At least one measurable lesion according to the Response Evaluation Criteria for
Solid Tumors (RECIST) criteria; for patients who only have bone metastases, an
evaluable non-irradiated lytic lesion is required
- Performance Status (WHO): PS ≤ 2 (Appendix 1).
- Laboratory tests in accordance with the following criteria:
Neutrophils ≥ 2x109/l,Platelets ≥ 100x109/l,Hemoglobin ≥ 10 g/dl, ASAT, ALAT ≤ 2.5 N , or
< 5 N when liver metastasis,bilirubin ≤ 1.5 N creatinin ≤ 1.5 N
- Signed, written consent before any study-related procedure
- Pre-menopausal patients who are not receiving concurrent LHRH agonist therapy
- ER- and PR-negative patients
- Contraindication to antiestrogens (thromboembolic risk) or ZARNESTRA
- Non metastatic tumor susceptible to management by radiotherapeutic and/or surgical
- T4d inflammatory tumor (PEV 2 or 3).
- Short-term, life-threatening lesions: hepatic invasion > 1/3 of liver volume,
pulmonary lymphangitis, uncontrolled cerebral metastases, carcinomatous meningitis
- Sensory neuropathy > or = grade 1 (WHO)
- Previous history of uncontrolled cancers or controlled for less than 5 years, except
basal cell skin cancers and in situ cancers of the cervix.
- Chronic diseases (somatic or psychiatric) with a poor prognosis
- subjects with enzyme-inducing anti-convulsants (e.g., phenytoin, phenobarbital,
carbamazepine) : this treatment is not permitted while taking ZARNESTRA
- Patients who, for family, social, geographic or psychological reasons, could not be
followed up correctly.