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Phase II Treatment of Metastatic Breast Cancer With Fulvestrant or Tamoxifen

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Rachel Jankowitz, University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Rachel Jankowitz, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02913430
First received: September 1, 2016
Last updated: July 19, 2017
Last verified: July 2017
  Purpose
To study progression free survival for treatment with Fulvestrant compared to treatment with tamoxifen in Metastatic Breast Cancer.

Condition Intervention Phase
Metastatic Breast Cancer Drug: Fulvestrant Drug: Tamoxifen Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Metastatic Breast Cancer With Fulvestrant or Tamoxifen: A Randomized Phase II Trial With ESR1 Mutation Tested in Circulating Tumor DNA.

Resource links provided by NLM:


Further study details as provided by Rachel Jankowitz, University of Pittsburgh:

Primary Outcome Measures:
  • Co-primary objectives to compare progression-free survival (PFS) in fulvestrant and tamoxifen arms in patients unselected by ESR1 mutation, and in the subset of patients with ESR1-mt tumors assessed primarily from ctDNA at enrollment. [ Time Frame: 6 months after last subject is enrolled ]
    PFS is defined as the duration of time from time of randomization to time of progression or death, whichever occurs first. PFS for a subject without an event will be censored on the date of last tumor assessment. If an interval of 6 months passes without a tumor assessment, PFS will be censored at the time of the earlier tumor assessment, even if an event (progressive disease or death) is later observed.


Secondary Outcome Measures:
  • Response rate compared between the tamoxifen and fulvestrant arms in the entire cohort and in the ESR1-mt [ Time Frame: 6 months after last patient enrolled ]
  • Overall Survival compared between the tamoxifen and fulvestrant arms in the entire cohort and in the ESR1-mt [ Time Frame: 5 years after study entry, or until all patients deceased ]
  • Number of participants with treatment-related adverse events as assessed by CTCAE v. 4.0 in each treatment arm [ Time Frame: while on study treatment, estimate 6 months from study entry in all patients ]
    Treatment related adverse events will be assessed in all patients as assessed by CTCAE v4.0. This will be determined at the monthly visits.

  • Clinical benefit rate (defined as CR+PR+ stable disease at any tumor assessment) and clinical benefit rate at 6 months (CBR6) (defined as CR+PR+ stable disease for at least 6 months) [ Time Frame: 6 months after last subject is enrolled ]

Other Outcome Measures:
  • Assessment of concordance of ESR1 status in plasma and biopsy samples [ Time Frame: 6 months after last subject is enrolled ]
  • Assessment of longitudinal changes in circulating levels of ESR1-mt and correlation with response [ Time Frame: 6 months after last subject is enrolled ]
  • Assessment of concordance with metastatic biopsies and archived primary tumor samples, determination of ESR1 status at diagnosis in archived tumor samples. [ Time Frame: 6 months after last subject is enrolled ]
  • Assessment of the functionality of ESR1 in tumor biopsies collected prior to and following treatment with fulvestrant as assessed by RNAseq [ Time Frame: 12 months after last subject is enrolled ]

Estimated Enrollment: 150
Study Start Date: October 2016
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
fulvestrant administered 500mg IM Q28 days
Drug: Fulvestrant
500mg IM Q28 days
Active Comparator: Arm B
Tamoxifen is administered orally, at a dose of20mg PO Qdaily
Drug: Tamoxifen
20mg PO Qdaily

Detailed Description:

The primary objectives are to compare progression-free survival (PFS) in fulvestrant and tamoxifen arms in patients unselected by ESR1 mutation, and in the subset of patients with ESR1-mt tumors assessed primarily from ctDNA at enrollment.

Patients with ER+ breast cancer who had 1 to 3 prior lines of endocrine therapy and up to one line of chemotherapy for MBC, excluding fulvestrant and tamoxifen, will be randomized in a 1:1 ratio to receive fulvestrant 500mg IM Q28 days with one extra dose on D15 of the first cycle (as a loading dose) or tamoxifen 20mg PO daily.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent
  2. Patients must have histologically or cytologically confirmed invasive breast cancer that is ER+ (>1% staining) with radiographical or clinical evidence of metastatic disease

    a. Measurable and/or non-measurable disease

  3. Prior therapies:

    1. Patients must have previously received an aromatase inhibitor in the adjuvant, neo-adjuvant or metastatic setting.
    2. The minimum duration of AI in the adjuvant setting is 2 years.
    3. There is no minimum duration of AI in the metastatic setting or neoadjuvant setting.
    4. Patients may have been previously treated with a CDK 4/6 inhibitor or mTOR inhibitor or other investigational agent in addition to an aromatase inhibitor.
    5. Prior treatment with tamoxifen is allowed in the adjuvant setting provided that it was followed by a minimum of 2 years of an AI.
  4. Brain metastasis allowed if previously treated, stable and off steroids for a minimum of 56 days
  5. Age > 18 years
  6. Male or female breast cancer is allowable
  7. Patients may be pre- or post-menopausal; pre-menopausal patients must be on ovarian suppression and must be adequately suppressed on LHRH agonists with estradiol levels in the post-menopausal range

    a. Premenopausal patients cannot be pregnant and must agree to adequate birth control in addition to ovarian suppression. Agreement by the patient and/or partner to use highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception. Contraception use should continue during the duration of study treatment and for at least 6 months after the last dose of study treatment.

  8. ECOG performance status 0-2
  9. Adequate bone marrow function as indicated by the following, within 14 days of enrollment:

    1. ANC ≥ 1500 cells/mm3
    2. Platelets ≥ 100,000 cells/ mm3
    3. Hemoglobin ≥ 9 g/dL
  10. Adequate liver function, as indicated by the following, within 14 days of enrollment.

    1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
    2. AST ≤ 1.5 x ULN
    3. ALT ≤ 2.5 x ULN
    4. Alkaline phosphatase ≤ 2.5 x ULN with the following exception; ALP ≤ 5× ULN in patients with bone metastases.
  11. Adequate hemostatic function as determined by PT, INR and aPTT < 1.5× ULN (unless on therapeutic coagulation, in which case the adequate level of anticoagulation will be determined by the investigator).
  12. Adequate renal function, as indicated by creatinine ≤ 1.5 x ULN.

Exclusion Criteria:

  1. Prior therapy exclusions:

    1. Prior therapy with fulvestrant
    2. Prior therapy with tamoxifen in the metastatic setting
    3. More than 3 prior lines of endocrine therapy in the metastatic setting
    4. More than one prior line of chemotherapy in the metastatic setting
  2. Washout of 2 weeks is required for aromatase inhibitors; washout of 4 weeks is required for CDK 4/6 inhibitor, everolimus or other biological agent.
  3. Patients must not be receiving any other investigational agent.
  4. Patients with symptomatic, untreated CNS metastases are not eligible.
  5. Patients may not have significant concurrent illness, infection, pregnancy or lactation
  6. Patients must not have a different active malignancy, except for skin basal cell carcinoma, skin squamous cell carcinoma and cervical intraepithelial neoplasia.
  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: NCT02913430

Contacts
Contact: Shannon L. Cieply 412-641-2357 cieplysl2@upmc.edu

Locations
United States, Pennsylvania
Magee-Womens Hospital UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Shannon L. Cieply    412-641-2357      
Sponsors and Collaborators
Rachel Jankowitz
  More Information

Responsible Party: Rachel Jankowitz, Assistant Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02913430     History of Changes
Other Study ID Numbers: 16-015
Study First Received: September 1, 2016
Last Updated: July 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Fulvestrant
Estradiol
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists
Estrogens
Hormones

ClinicalTrials.gov processed this record on August 18, 2017