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Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

Primary Purpose

Breast Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Enzalutamide
Fulvestrant
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring ER+/Her2 - breast cancer, Preoperative Fulvestrant, Enzalutamide

Eligibility Criteria

18 Years - 101 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • ER+ Her2- breast cancer
  • Stage at least T2 or greater
  • Planned to get local surgery
  • Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression.
  • At least 18 years of age
  • Not on anticoagulants
  • PS 0-2
  • Able to swallow study drug and comply with study requirements
  • ANC >1000/uL, platelets >75,000/uL at screening visit
  • Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or < 5 times ULN if patient has documented liver metastases
  • Creatinine < 1.5 times ULN
  • INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy
  • Willing to donate blood for research at 4 time points
  • Willing to undergo core biopsies for research at study entry and at ~4 weeks.
  • Willing to donate tissue to research from the surgical specimen
  • Written informed consent obtained prior to biopsies and blood samples

Exclusion Criteria:

  • Current or previously treated brain or leptomeningeal metastases
  • History of seizures
  • Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464).
  • Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal estrogens are allowed if necessary for patient comfort.

Sites / Locations

  • University of Colorado
  • Memorial Sloan Kettering Cancer Center
  • West Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Fulvestrant Without Enzalutamide

Fulvestrant With Enzalutamide

Arm Description

500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)

500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC), plus160mg of Enzalutamide will be given daily.

Outcomes

Primary Outcome Measures

Number of Patients With a PEPI Score Equal to Zero at Post Treatment
The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence. PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and >= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better.

Secondary Outcome Measures

Disease-free Survival
Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate
To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects.
Androgen Receptor (AR) Expression
The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.

Full Information

First Posted
November 1, 2016
Last Updated
May 23, 2023
Sponsor
University of Colorado, Denver
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT02955394
Brief Title
Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
Official Title
Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 21, 2017 (Actual)
Primary Completion Date
February 17, 2023 (Actual)
Study Completion Date
February 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after ~4 months on treatment.
Detailed Description
This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after ~4 months on treatment. After consent, all patients will get a tissue biopsy, and than half the patients will get fulvestrant alone (standard dosing) and the other half of the patients will get fulvestrant plus enzalutamide. At ~4 weeks, a biopsy will be done and therapy will be continued. Hormone therapy will continue for ~4 months at which point the patients will undergo surgical resection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
ER+/Her2 - breast cancer, Preoperative Fulvestrant, Enzalutamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fulvestrant Without Enzalutamide
Arm Type
Placebo Comparator
Arm Description
500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Arm Title
Fulvestrant With Enzalutamide
Arm Type
Experimental
Arm Description
500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC), plus160mg of Enzalutamide will be given daily.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
MDV3100
Intervention Description
160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
FASLODEX
Intervention Description
500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Primary Outcome Measure Information:
Title
Number of Patients With a PEPI Score Equal to Zero at Post Treatment
Description
The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence. PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and >= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better.
Time Frame
16 Weeks
Secondary Outcome Measure Information:
Title
Disease-free Survival
Description
Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
Time Frame
15 months
Title
Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate
Description
To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects.
Time Frame
4 years
Title
Androgen Receptor (AR) Expression
Description
The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.
Time Frame
16 Weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
101 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ER+ Her2- breast cancer Stage at least T2 or greater Planned to get local surgery Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression. At least 18 years of age Not on anticoagulants PS 0-2 Able to swallow study drug and comply with study requirements ANC >1000/uL, platelets >75,000/uL at screening visit Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or < 5 times ULN if patient has documented liver metastases Creatinine < 1.5 times ULN INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy Willing to donate blood for research at 4 time points Willing to undergo core biopsies for research at study entry and at ~4 weeks. Willing to donate tissue to research from the surgical specimen Written informed consent obtained prior to biopsies and blood samples Exclusion Criteria: Current or previously treated brain or leptomeningeal metastases History of seizures Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464). Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal estrogens are allowed if necessary for patient comfort.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony D Elias, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
West Cancer Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21552212
Citation
Collins LC, Cole KS, Marotti JD, Hu R, Schnitt SJ, Tamimi RM. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses' Health Study. Mod Pathol. 2011 Jul;24(7):924-31. doi: 10.1038/modpathol.2011.54. Epub 2011 May 6.
Results Reference
background
PubMed Identifier
25904752
Citation
Elebro K, Borgquist S, Simonsson M, Markkula A, Jirstrom K, Ingvar C, Rose C, Jernstrom H. Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort. Clin Cancer Res. 2015 Aug 15;21(16):3640-50. doi: 10.1158/1078-0432.CCR-14-2564. Epub 2015 Apr 22.
Results Reference
background
PubMed Identifier
21325075
Citation
Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011 Apr 1;17(7):1867-74. doi: 10.1158/1078-0432.CCR-10-2021. Epub 2011 Feb 15.
Results Reference
background
PubMed Identifier
24451109
Citation
Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D'Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gomez F, Medicherla S, Alfaro IE, McCullagh E, Jedlicka P, Torkko KC, Thor AD, Elias AD, Protter AA, Richer JK. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res. 2014 Jan 22;16(1):R7. doi: 10.1186/bcr3599.
Results Reference
background
PubMed Identifier
27565181
Citation
D'Amato NC, Gordon MA, Babbs B, Spoelstra NS, Carson Butterfield KT, Torkko KC, Phan VT, Barton VN, Rogers TJ, Sartorius CA, Elias A, Gertz J, Jacobsen BM, Richer JK. Cooperative Dynamics of AR and ER Activity in Breast Cancer. Mol Cancer Res. 2016 Nov;14(11):1054-1067. doi: 10.1158/1541-7786.MCR-16-0167. Epub 2016 Aug 26.
Results Reference
background
PubMed Identifier
20228125
Citation
Takagi K, Miki Y, Nagasaki S, Hirakawa H, Onodera Y, Akahira J, Ishida T, Watanabe M, Kimijima I, Hayashi S, Sasano H, Suzuki T. Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment. Endocr Relat Cancer. 2010 Apr 21;17(2):415-30. doi: 10.1677/ERC-09-0257. Print 2010 Jun.
Results Reference
background
Citation
Elias A, Richer JK, LoRusso P, Peterson AC, Steinberg J, Mordenti J, Lopez C, Hudis C, Traina T. MDV3100-08: A phase 1 open-label, dose-escalation study evaluating the safety, tolerability, and pharmacokinetics of MDV3100 in women with incurable breast cancer. ASCO 2012, TPS668
Results Reference
background
PubMed Identifier
22894553
Citation
Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.
Results Reference
background
PubMed Identifier
26255746
Citation
Yeo B, Dowsett M. Neoadjuvant endocrine therapy: Patient selection, treatment duration and surrogate endpoints. Breast. 2015 Nov;24 Suppl 2:S78-83. doi: 10.1016/j.breast.2015.07.019. Epub 2015 Aug 6.
Results Reference
background
PubMed Identifier
23891267
Citation
Charehbili A, Fontein DB, Kroep JR, Liefers GJ, Mieog JS, Nortier JW, van de Velde CJ. Neoadjuvant hormonal therapy for endocrine sensitive breast cancer: a systematic review. Cancer Treat Rev. 2014 Feb;40(1):86-92. doi: 10.1016/j.ctrv.2013.06.001. Epub 2013 Jul 23.
Results Reference
background
PubMed Identifier
17538978
Citation
Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007 Jul 15;110(2):244-54. doi: 10.1002/cncr.22789.
Results Reference
background
PubMed Identifier
21042932
Citation
von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S, Fasching PA, Eiermann W, Blohmer JU, Costa SD, Mehta K, Hilfrich J, Jackisch C, Gerber B, du Bois A, Huober J, Hanusch C, Konecny G, Fett W, Stickeler E, Harbeck N, Muller V, Juni P. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011 Jan;125(1):145-56. doi: 10.1007/s10549-010-1228-x. Epub 2010 Nov 3.
Results Reference
background
PubMed Identifier
16622270
Citation
Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006 Apr 20;24(12):1940-9. doi: 10.1200/JCO.2005.02.6187. Erratum In: J Clin Oncol. 2006 Jul 1;24(19):3221.
Results Reference
background
PubMed Identifier
15701892
Citation
Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, Griffith C, Boeddinghaus I, Salter J, Detre S, Hills M, Ashley S, Francis S, Walsh G; IMPACT Trialists. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res. 2005 Jan 15;11(2 Pt 2):951s-8s.
Results Reference
background
PubMed Identifier
17912634
Citation
Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105 Suppl 1(Suppl 1):33-43. doi: 10.1007/s10549-007-9701-x. Epub 2007 Oct 3. Erratum In: Breast Cancer Res Treat. 2008 Nov;112(2):371.
Results Reference
background
PubMed Identifier
26371134
Citation
Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiowka M, Hewson N, Rukazenkov Y, Robertson JF. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. J Clin Oncol. 2015 Nov 10;33(32):3781-7. doi: 10.1200/JCO.2015.61.5831. Epub 2015 Sep 14.
Results Reference
background
PubMed Identifier
23065000
Citation
Robertson JF, Lindemann JP, Llombart-Cussac A, Rolski J, Feltl D, Dewar J, Emerson L, Dean A, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized 'FIRST' study. Breast Cancer Res Treat. 2012 Nov;136(2):503-11. doi: 10.1007/s10549-012-2192-4. Epub 2012 Oct 13.
Results Reference
background
PubMed Identifier
2702835
Citation
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
Results Reference
background

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Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

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