A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients

Study Overview
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Brief Summary
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This is a dosage escalation study to estimate the maximum tolerated dose of 9-cis-retinoic acid given in combination with tamoxifen. Groups of 3 to 6 patients receive oral 9-cis-retinoic acid daily for 4 weeks, after which daily oral tamoxifen is added to the regimen. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate.

Detailed Description
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This is a Phase I study of the combination tamoxifen and 9-cis-Retinoic acid in patients with breast cancer. The primary objective of the study is; 1) to determine the maximum tolerated dose of 9-cis-Retinoic acid in combination with Tamoxifen and to determine the overall and dose limiting toxicities. Other objectives are: 2) to determine the effect of Tamoxifen on the pharmacokinetics of 9-cis-Retinoic acid; 3) to evaluate the anti-tumor activity of this combination therapy within the context of a phase I study; 4) and to determine the expression of surrogate biomarkers of breast carcinogenesis before and after treatment.

Official Title
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A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients

Conditions
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Breast Cancer, Breast Neoplasm

Intervention / Treatment
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* Drug: 9-cis-Retinoic Acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: All patients must have histologically documented diagnosis of Stage III, or IV breast carcinoma. Patients with stage III that has completed chemotherapy: Estrogen receptor (ER) or progesterone receptor (PR) positive tumor required if premenopausal. Either ER/PR-positive or -negative tumor allowed if postmenopausal and have received prior chemotherapy. Patients may have stage IV with ER/PR-positive or -negative tumor. No CNS metastases, pseudotumor cereri, or seizures. PRIOR/CONCURRENT THERAPY: Patients who have ecovered from the toxic effects of prior therapy will be eligible. Patients with prior tamoxifen will be allowed to participate. At least 3 weeks must have elapsed since the last dose of chemotherapy. PATIENT CHARACTERISTICS: Age: 18 and over. Sex: Men and women. Menopausal status: Any status. Patients must have a performance status of ECOG 0-2. Patients must have Hematopoietic criteria of: ANC at least 1,500/mm(3). Platelet count at least 90,000/mm(3). Patients must have Hepatic criteria of: In the absence of tumor involvement: Bilirubin no greater than twice normal; SGOT no greater than twice normal; Alkaline phosphate no greater than twice normal; Fasting triglycerides less than 3 times normal. Patients must have Renal criteria of: Serum creatinine no greater than 1.5 mg/dL OR; Creatinine clearance at least 60 mL/min. Other: No allergy to study medications. No nonmalignant systemic disease that would preclude therapy. No second malignancy within 5 years except: Curatively treated basal cell skin carcinoma. Cervical carcinoma in situ. Pregnant women will be excluded. Negative pregnancy test required within 7 days prior to entry. Adequate contraception required for 4 weeks prior to, during, and for 1 year after study. Patients must give informed consent. Patients who are poor medical or psychiatric risks will be eligible.
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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 9-cis-Retinoic Acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinoids, Biomarkers