Trial record 1 of 1 for:    NCT00324259
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Study of Physiological and High Dose Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00324259
First received: May 8, 2006
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

This study aims to examine whether estradiol is an appropriate for future Phase 3 studies as second or third line endocrine treatment. In addition the protocol explores several approaches to enhance the safety of estrogen therapy, including the establishment of the efficacy of a lower dose than that currently recommended and through the early identification of non-responders to avoid drug exposure in patients who are unlikely to benefit to estrogen treatment.


Condition Intervention Phase
Breast Neoplasms
Drug: Estradiol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Study of Physiological (6 mg Daily) and High Dose (30 mg Daily) Estradiol in the Treatment of Hormone Receptor Positive Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Clinical benefit rate (CR plus PR plus SD) in patients with advanced breast cancer using intermediate (6 mg) and high (30 mg) daily doses of oral estradiol. [ Time Frame: 24 weeks after treatment ] [ Designated as safety issue: No ]
    SD is defined as lack of disease progression by 24 weeks.


Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Until patient death ] [ Designated as safety issue: No ]
  • Assess the impact of both doses of estrogen on the quality of life in patients with advanced breast cancer. [ Time Frame: Baseline, Day 28, and end of study treatment ] [ Designated as safety issue: No ]
  • Assess the frequency of response to re-treatment with the same aromatase inhibitor that immediately preceded treatment with estradiol on protocol. [ Time Frame: 12 weeks post-treatment termination ] [ Designated as safety issue: No ]
  • Assess the frequency of response to re-treatment with estradiol for patients who have a secondary response to an aromatase inhibitor after the first response to estradiol. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Until patient death ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: August 2004
Study Completion Date: August 2014
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
6 mg of estradiol daily (2 mg tid).
Drug: Estradiol
Active Comparator: Arm 2
30 mg of estradiol. (10 mg tid)
Drug: Estradiol

Detailed Description:

The purpose of this study is to compare the effects of two doses (6 mg and 30 mg) of Estradiol, a type of estrogen. This and other forms of estrogen used at doses much higher than those used for postmenopausal hormone replacement therapy have been shown to cause tumor growth stabilization or shrinkage in patients with breast cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal women with advanced hormone receptor positive (ER and or PgR) breast cancer, has received prior treatment with an aromatase inhibitor in the advanced disease setting, and experienced at least 24 weeks of progression free survival. As long as the patient experienced an aromatase inhibitor response as defined this way, she is still eligible even if she has received further lines of endocrine therapy, which may include other aromatase inhibitors or tamoxifen, even if these subsequent lines of treatment were unsuccessful (see below for permitted chemotherapy and trastuzumab therapy).

OR

  • Postmenopausal women with systemic or unresectable local relapse after taking at least two years of adjuvant aromatase inhibitor therapy.
  • Clinical diagnosis of postmenopausal status is defined as either:

    1. Age greater than 50 years and amenorrhea for 1 year
    2. Bilateral Surgical ovariectomy
    3. Serum FSH and estradiol level in the postmenopausal range before the initiation of AI therapy.
    4. If the patient was receiving an LHRH agonist to maintain a postmenopausal state during AI therapy this should be continued since recovery of menses would lead to uncontrolled estrogen exposure and pregnancy during estrogen therapy is contraindicated.
  • Tumor cell expression of ER and/or PgR can be ascertained on either the primary or the metastatic site. However when both types of tissue are available, the metastatic site should be used to determine eligibility. ER and/or PgR positive are defined as at least 10% of malignant cells with positive nuclear staining.
  • The patients may have received adjuvant and/or neoadjuvant chemotherapy.
  • Prior radiotherapy is permitted as long as it was planned before the start of the study medication and is completed within 3 weeks of trial medication starting.
  • Prior tamoxifen therapy is also permitted as adjuvant or advanced disease therapy.
  • Patients with ER+ HER2+ disease are eligible even of they have received trastuzumab in the past (and even if it was administered in combination with endocrine treatment) as long as they meet all other eligibility criteria. Trastuzumab therapy must be held during estradiol treatment.
  • Use of prior experimental agents alone or in combination with endocrine therapy is also permissible, but a wash out of one month is required if the immediate prior therapy involved a study medication that had not been subject to regulatory approval.
  • Prior adjuvant chemotherapy is permitted as well as one line of chemotherapy for advanced disease.
  • Patient must have at least one measurable lesion defined by RECIST criteria. To be considered measurable, a baseline lesion must have a minimum diameter to compensate for measurement error: 1 cm for soft tissue lesions, 1 cm for lung lesions including pleural lesions measured by CT scan, 1 cm for liver lesions measured by CT scan.
  • Patients with bone only disease can also be enrolled if they meet the following criteria:

    1. Four or more lesions more than one cm, measurable on CT scan bone windows.
    2. At least one tumor marker that is elevated to at least two times the upper limit of normal.
    3. All patients should have a baseline bone scan with X-ray evaluation of all hot spots, CT chest abdomen and pelvis (with bone windows), and tumor marker assessment. Also CT scan of the extremities should be done on suspicious areas seen on X-ray evaluation of all hot spots if these extremity lesions are to be followed for response.
  • The patient must have an ECOG performance status of 0-2
  • The patient should have a life expectancy of > 6 months.
  • The patient must have adequate hematologic function, defined as ANC >1000/mm3 and platelets > 75,000/mm3.
  • The patient must have adequate renal function, defined as serum creatinine less than or equal to 1.5 times the upper limit of normal.
  • The patient must have adequate liver function defined as serum bilirubin less than or equal to 1.5 times the upper limit of normal (three times the upper limit of normal for patients with hereditary benign hyperbilirubinaemia), transaminases (ALT, AST) less than or equal to 2.5 times the upper limit of normal in patients without liver metastasis or less than or equal to 5 times the upper limit of normal in patients with liver metastasis.
  • For patients with bone metastasis, treatment with i.v. bisphosphonates during the trial is mandatory because of the risk of hypercalcemia. Bisphosphonate therapy must be started before the patient begins protocol therapy.
  • Preexisting hypercalcemia should be treated and calcium normalized prior to study entry.
  • The patient must give written informed consent prior to initiation of any invasive study-related procedures that would otherwise not be performed, and must be able to comply with scheduled visits and evaluations.
  • Inclusion of Women and Minorities: Entry to this study is open to women of all racial and ethnic subgroups.
  • Patients with fasting blood glucose level ≤ 200 mg/dL. If greater, hyperglycemia must be treated before initiation of study investigations.

Exclusion Criteria:

  • Patients with CNS involvement with metastatic breast cancer or life threatening lymphangitic or large volume lung or liver disease that threatens organ function.
  • Patients with history of deep venous thrombosis, pulmonary embolism, stroke, acute myocardial infarction, congestive cardiac failure, untreated hypertension.
  • Ischemic changes on a baseline EKG or other evidence of ischemic heart disease.
  • Undiagnosed abnormal genital bleeding
  • Untreated cholelithiasis
  • Fasting serum triglycerides greater than 400. Patients should be treated and triglycerides controlled prior to study entry.
  • Treatment with fulvestrant within 12 months of study initiation (fulvestrant has been shown to antagonize estradiol induced apoptosis in preclinical models (5).
  • The patient's only qualifying lesion (s) have been previously irradiated or are scheduled for irradiation following study entry.
  • Severe or uncontrolled concomitant disease from other causes.
  • EGOG Performance status 3 or 4.
  • The patient has previous malignancies other than breast cancer except a) adequately treated in situ carcinoma of the cervix, b) localized basal or squamous cell carcinoma of the skin c) any previous malignancy treated with curative intent with a recurrence risk of less than 30%.
  • The patient is unable to understand the informed consent or is unlikely to be compliant with the protocol.
  • More than one line of palliative chemotherapy for advanced disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324259

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina Breast Clinic
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western University
Cleveland, Ohio, United States, 44106
Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Matthew Ellis, M.D., Ph.D. Washington University Early Recognition Center
  More Information

Additional Information:
No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00324259     History of Changes
Other Study ID Numbers: 04-0412 / 201108392
Study First Received: May 8, 2006
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Polyestradiol phosphate
Contraceptive Agents
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014