Abstract OT3-2-06: TREND: A randomized phase II clinical trial evaluating the endocrine activity and efficacy of neoadjuvant degarelix versus triptorelin in premenopausal patients receiving letrozole for locally advanced endocrine responsive breast cancer (IBCSG 41-13)
Authors: Dellapasqua S , Colleoni M , Maibach R 
Published: August 2014

Background

The TREND trial compares endocrine activity of neoadjuvant triptorelin (Trip) and degarelix (Deg) in premenopausal patients receiving letrozole for primary endocrine responsive breast cancer. Recent studies suggest that combined neoadjuvant endocrine therapy with GnRH analogues and aromatase inhibitors (AIs) is effective for a selected group of premenopausal patients; degarelix, a GnRH antagonist, may induce faster ovarian suppression compared with other GnRH analogues.

Trial Design

This randomized phase II trial compares Trip and Deg in terms of time to optimal ovarian function suppression (OFS). The primary endpoint is defined as time from the first injection of Trip or Deg to the first assessment of centrally assessed 17-β-estradiol (E2) level in the range of optimal ovarian function suppression (≤2.72 pg/mL or ≤10 pmol/L) during the 6 cycles of neoadjuvant treatment. All patients receive 6 28-day cycles of neoadjuvant therapy: Trip: 3.75mg i.m. on day 1 of each cycle; Deg: 240mg s.c. cycle 1 day 1 and 80mg s.c. cycles 2-6 day 1. All patients receive 2.5mg/day continuous letrozole for all 6 cycles. Secondary endpoints include tolerability, Ki67 changes, preoperative endocrine prognostic index (PEPI) score, and best overall disease response.

Major Eligibility Criteria

• Premenopausal status confirmed (E2 &gt; 54 pg/mL (or above 198 pmol/L) within 14 days of randomization

• Histologically confirmed invasive breast cancer

• ER and PgR &gt; 50% of the cells and HER2-negative

• No hormonal treatment in previous 2 months

• No GnRH analogue, SERM or AI within 12 months prior to randomization

• Normal hematologic, renal, liver and cardiac function

Specific Aim

To compare the endocrine activity of neoadjuvant Deg and Trip in premenopausal patients also receiving letrozole.

Statistical Methods

Randomized patients receiving at least one injection in both arms will be included in primary analysis. The primary endpoint will be evaluated in both treatment arms using stratified two-sample log-rank test (two-sided Type I error) with age as stratification factor. Assuming accrual of 25 patients per treatment arm (2 patients/month over approx. 24 months), the trial will have at least 90% power to detect a targeted or pre-specified difference in time to optimal OFS. Kaplan Meier method will be used to estimate distribution of the primary endpoint.

Accrual: Target: 50 (Arm A: 25; Arm B: 25); Present: 0

Translational research

A tumor block from the diagnostic core biopsy and one from final surgery will be collected and banked for central review and future translational research.

Patient Reported Symptoms (PRS)

PRS scores will be measured at baseline, day 1 of cycles 2 and 4 and prior to surgery. E2 will be correlated with the PRS scores. Individual endocrine symptoms (FACT-ES) will be summarized over time.

Contact Information

The TREND trial is conducted and sponsored by the International Breast Cancer Study Group (IBCSG). Contact Dr. Rudolf Maibach, IBCSG Coordinating Center, Bern, Switzerland, rudolf.maibach@ibcsg.org, or the Trial Coordinators at ibcsg41_TREND@fstrf.org.

Pharmaceutical Support: Ferring.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-2-06.