NCT02188745: POLLY

ER Reactivation Therapy for Breast Cancer

Completed Phase 2 Last updated 17 July 2024

What this trial tests

Phase 2 trial testing 17B-estradiol in Metastatic Breast Cancer in 19 participants. Completed in 5 July 2024.

Timeline

11 March 2016

Primary endpoint
5 January 2024

5 July 2024

Quick facts

Lead sponsor	Dartmouth-Hitchcock Medical Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	11 March 2016
Primary completion	5 January 2024
Estimated completion	5 July 2024
Sites	3 locations across United States

Drugs / interventions tested

• 17B-estradiol
• Letrozole — full drug profile →
• Anastrozole (anastrozole) — full drug profile →
• Exemestane (exemestane) — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →

Sponsor

Dartmouth-Hitchcock Medical Center

Who can join

18 and older, female only, with Metastatic Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Before anti-estrogens such as tamoxifen were developed to treat estrogen receptor (ER)-positive breast cancer, high-dose estrogen therapies were used. This seems counterintuitive since anti-estrogens block ER function, while estrogens increase ER function, but these therapies are effective to similar extents for the treatment of metastatic ER+ breast cancer. Estrogen therapies are most effective against cancers that develop resistance to anti-estrogens, likely because such cancers have adapted to grow without ER function, and restoring ER function (with estrogen) is damaging to the cancer cells. In some patients with ER+ breast cancer that becomes resistant to anti-estrogens, treatment with the estrogen 17B-estradiol induces tumor response. Furthermore, when 17B-estradiol-sensitive tumors eventually become resistant to 17B-estradiol, switching back to anti-estrogen therapy is often effective. These observations suggest that cancers can alternate between anti-estrogen-sensitive and 17B-estradiol-sensitive states. The investigators hypothesize that treatment with alternating 17B-estradiol / anti-estrogen therapies on a defined 8-week / 16-week schedule will more effectively prevent cancer growth than continuous treatment with either type of therapy in patients with metastatic anti-estrogen-resistant ER+ breast cancer.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer.
   Traphagen NA, Schwartz GN, Tau S, Roberts AM, et al · · 2023 · cited 16× · PMID 37439680 · DOI 10.1158/1078-0432.ccr-23-0488
2. Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer.
   Schwartz GN, Kaufman PA, Giridhar KV, Marotti JD, et al · · 2023 · cited 8× · PMID 37260292 · DOI 10.1158/1078-0432.ccr-23-0112