NCT04113863

Evaluation of ATRA Activity in Combination With Anastrozole in Pre-operative Phase of Operable Early Breast Cancer

A Randomized Phase 2 Clinical Trial to Evaluate the Activity of ATRA in Combination With Anastrozole in Pre-operative Phase of Operable HR-positive/HER2-negative Early Breast Cancer (ATRA)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (actual)
• Sponsor: Mario Negri Institute for Pharmacological Research · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is an Italian, single center, randomized, phase II study. ATRA (all-trans retinoic acid) and derivatives (retinoids) are promising anticancer agents and exert their anti-proliferative, differentiating and apoptotic effects through the nuclear retinoic acid receptors, including RARα (retinoic acid receptor alpha). Although the clinical use of ATRA in haematological malignancies (Acute Promyelocytic Leukemia, APL) is well established, its use in solid tumors is limited. However, some recent pre-clinical evidence suggests a possible role of ATRA in the treatment of specific subtypes of HR-positive (Hormonal Receptor)/HER2-negative early breast cancer (eBC). Moving from pre-clinical evidence and given the well-known retinoid mechanism of action, The hypotheses is that ATRA contributes to tumor regression in a specific sub-population of eBCs. Using a preoperative "window-of-opportunity" model, aimed at testing the activity of ATRA in combination with anastrozole in postmenopausal women with newly diagnosed, resectable, HR+/HER2- eBCs.

Detailed description

This is an Italian, single center, randomized, phase II study. ATRA (all-trans retinoic acid) and derivatives (retinoids) are promising anticancer agents and exert their anti-proliferative, differentiating and apoptotic effects through the nuclear retinoic acid receptors, including RARα (retinoic acid receptor alpha). Although the clinical use of ATRA in haematological malignancies (Acute Promyelocytic Leukemia, APL) is well established, its use in solid tumors is limited. However, some recent pre-clinical evidence suggests a possible role of ATRA in the treatment of specific subtypes of HR-positive (Hormonal Receptor)/HER2-negative early breast cancer (eBC). This is a prospective, randomized Phase 2 window-of opportunity pre-operative clinical trial to study the activity of ATRA in combination with anastrozole in HR+/HER2- eBCs. All patients will receive primary treatment with anastrozole p.o. (intended as standard of care) and will be randomized to add or not ATRA p.o. Patients will receive study treatments by continuous once-daily administration for a period of 4 weeks before definitive surgery. Treatment will start 28 days before the scheduled surgical resection and will be completed at the time of surgery, scheduled no more than 1 week after completion of the study treatment. The interval between diagnostic core biopsy, baseline clinical evaluation and study entry must be no more than 4 weeks. The study will compare the anti-tumor activity of the treatments in the two arms (ATRA+anastrozole or Aa vs. anastrozole alone or a). In this comparison, the primary outcome measure is the proportion of complete BC cells cycle arrest (defined as Ki67 \< 2.7%), as previously reported. Indeed, the responder patients will be defined according the achievement of an absolute value of Ki67 \< 2.7% because of its predictive value on relapse-free survival. The study aims at demonstrating that the ATRA+anastrozole (Aa) arm is characterized by significant therapeutic superiority over the anastrozole (a) arm. Clinical and ultrasound examinations, trascriptome analysis on formalin-fixed paraffin-embedded (FFPE) samples will be performed, at baseline and at the time of definitive surgery

Conditions

• Breast Neoplasm Female

Interventions

Type	Name	Description
DRUG	all-trans retinoic acid	Vesanoid will be supplied orally at the total dosage of 45mg/m2/d (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days
DRUG	Anastrozole 1mg	Anastrozole will be administered orally at the dosage of 1 mg/die.

Timeline

• Start date: 2019-06-18
• Primary completion: 2025-01-30
• Completion: 2025-01-30
• First posted: 2019-10-03
• Last updated: 2025-12-18

Locations

2 sites across 1 country: Italy