Clinical trial NCT00972023: DHEA in Treating Women Undergoing Surgery for Stage I, Stage II, or Stage III Breast Cancer
Official title: A Pilot Study of Androgen Receptor as a Target for the Treatment of ER-/PR-/AR + Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: triple-negative breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-09-04
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Dehydroepiandrosterone (DHEA) may slow the growth of tumor cells and be an effective treatment for women with breast cancer.

PURPOSE: This phase I trial is studying how well DHEA works in treating women undergoing surgery for stage I, stage II, or stage III breast cancer.

Detailed description: OBJECTIVES:

Primary

* To identify the effect of the adrenal steroid, dehydroepiandrosterone (DHEA), on tumor proliferation in women with estrogen receptor-negative, progesterone receptor-negative, HER2/neu-negative, and androgen receptor (AR)-positive stage I-III adenocarcinoma of the breast.

Secondary

* To study the effect of DHEA on expression of AR in these patients.
* To assess the effect of DHEA on changes in serum estrogen and androgen hormone levels (e.g., estrone, estradiol, testosterone, dihydrotestosterone, DHEA, and DHEA-sulfate) in these patients.
* To assess the toxicity of DHEA in these patients.
* To follow the clinical course of these patients.

OUTLINE: Patients receive oral dehydroepiandrosterone (DHEA) twice daily on days -14 to 0. Patients then undergo surgery on day 1.

Tissue samples are collected at baseline and at the time of surgery for biomarker analysis (androgen receptor, estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and p53) by IHC. Blood samples are collected at baseline and after completion of treatment with DHEA for analysis of serum hormone (e.g., estrone, estradiol, testosterone, dihydrotestosterone, DHEA, and DHEA-sulfate) and cytokine levels.

After completion of study therapy, patients are followed up at 1 week and then every 6 months for 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed invasive adenocarcinoma of the breast

  * Stage I (T1c), II, or III disease (AJCC staging system)

    * Lesion ≥ 1 cm on breast imaging studies (mammogram, ultrasound, or MRI)
* HER2/neu-negative tumor
* Planning to receive dehydroepiandrosterone (DHEA) prior to surgery
* Disease amenable to surgery with curative intent

  * Scheduled to undergo surgery immediately after completion of DHEA
* No locally advanced or metastatic disease not amenable to surgery
* Hormone receptor status:

  * Estrogen receptor- and progesterone receptor-negative tumor
  * Androgen receptor-positive tumor

PATIENT CHARACTERISTICS:

* Menopausal status not specified
* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* ANC ≥ 1,000/mm\^3
* Platelet count ≥ 75,000/mm\^3
* AST and ALT ≤ 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 2.5 times ULN
* Bilirubin ≤ 2 times ULN
* Hemoglobin \> 9 g/dL
* Creatinine normal OR creatinine clearance ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 1 week after completion of study therapy
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to DHEA or anastrozole
* No concurrent uncontrolled illness, including but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness or social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 5 years since prior surgery, radiotherapy, biological therapy, hormone therapy, and/or chemotherapy for invasive breast cancer
* No other concurrent antineoplastic or antitumor agents
* No other concurrent investigational agents

Primary outcomes:
measure: Tumor Proliferation (Percentage of Ki-67 Positive Cells)
timeFrame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
Secondary outcomes:
measure: Effect of Dehydroepiandrosterone (DHEA) on Androgen Receptor Expression
timeFrame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
measure: Effect of DHEA on Changes in Serum Estrogen and Androgen Hormone Levels (e.g., Estrone, Estradiol, Testosterone, Dihydrotestosterone, DHEA, and DHEA-sulfate)
timeFrame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
measure: Toxicity
timeFrame: Within 48 hours prior to surgery and after 14 days of DHEA treatment.
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Zeina Nahleh, MD
role: PRINCIPAL_INVESTIGATOR
References: