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

Breast Cancer Clinical Trial

Official title:

Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02955394
• Other study ID #: 16-1042.cc
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 21, 2017
• Est. completion date: February 2027

Study information

• Verified date: May 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 61
• Est. completion date: February 2027
• Est. primary completion date: February 17, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Enzalutamide
160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
• Fulvestrant
500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	West Cancer Center	Germantown	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (18)

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. — View Citation

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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. — View 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. — View Citation

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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

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. — View Citation

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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. — View 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. — View 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. — View Citation

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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. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 Weeks
Secondary	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.	15 months
Secondary	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.	4 years
Secondary	Androgen Receptor (AR) Expression	The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.	16 Weeks