A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer; Breast Neoplasm
Intervention: 9-cis-Retinoic Acid (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Cancer Institute (NCI)
Summary
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.
Clinical Details
Official title: A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients
Study design: Endpoint Classification: Safety Study, Primary Purpose: Treatment
Detailed description:
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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
National Cancer Institute (NCI), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Fontana JA. Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. Exp Cell Biol. 1987;55(3):136-44. Welsch CW, DeHoog JV. Retinoid feeding, hormone inhibition, and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas. Cancer Res. 1983 Feb;43(2):585-91. Jordan VC, Murphy CS. Endocrine pharmacology of antiestrogens as antitumor agents. Endocr Rev. 1990 Nov;11(4):578-610. Review.
Starting date: May 1996
Last updated: March 3, 2008
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