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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001504
• Other study ID #: 960080
• Secondary ID: 96-C-0080
• Status: Completed
• Phase: Phase 1
• First received: November 3, 1999
• Last updated: March 3, 2008
• Start date: May 1996
• Est. completion date: January 2002

Study information

• Verified date: January 2002
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasm
• Breast Neoplasms

Intervention

Drug:
• 9-cis-Retinoic Acid

Locations

Country	Name	City	State
United States	National Cancer Institute (NCI)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Fontana JA. Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. Exp Cell Biol. 1987;55(3):136-44. — View Citation

Jordan VC, Murphy CS. Endocrine pharmacology of antiestrogens as antitumor agents. Endocr Rev. 1990 Nov;11(4):578-610. Review. — View Citation

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. — View Citation