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

NCT04113863 | Terminated Phase 2

• 1 other identifier: RF-2016-02362383
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Neoplasm Female

Outcome Measures

Primary Outcomes (1)

• Responders

  Evaluate the proportion of responder patients in the 2 arm (Aa vs. a) according to the Ki67 assessment, measured at baseline and after treatment

  At time of surgery. Analyses will be performed approximately 24 months after the enrolment of the first patient, i.e. when all the 112 patients required by simple size specifications complete their treatment schedule and reach the surgical phase.

Secondary Outcomes (4)

• Ki67 reduction

  At time of surgery. Analyses will be performed approximately 24 months after the enrolment of the first patient, i.e. when all the 112 patients required by simple size specifications complete their treatment schedule and reach the surgical phase.

• ORR (Overall Response Rate)

  At time of surgery. Analyses will be performed approximately 24 months after the enrolment of the first patient, i.e. when all the 112 patients required by simple size specifications complete their treatment schedule and reach the surgical phase.

• ATRA-21

  At time of surgery. Analyses will be performed approximately 24 months after the enrolment of the first patient, i.e. when all the 112 patients required by simple size specifications complete their treatment schedule and reach the surgical phase.

• Safety evaluation

  Safety assessments will occur at day 1 (D1) and after 2 weeks (D14) and after 4 weeks (D28) during treatment.

Study Arms (2)

ARM A - Anastrozole

ACTIVE COMPARATOR

Anastrozole at the dosage of 1 mg/die. Treatment will last 28 days

Drug: Anastrozole 1mg

ARM B - Anastrozole + ATRA

EXPERIMENTAL

Anastrozole at the dosage of 1mg/die in combination with ATRA at the total dosage of 45mg/m2/die (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days

Drug: all-trans retinoic acid; Drug: Anastrozole 1mg

Interventions

all-trans retinoic acid DRUG

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

Also known as: Vesanoid

ARM B - Anastrozole + ATRA

Anastrozole 1mg DRUG

Anastrozole will be administered orally at the dosage of 1 mg/die.

ARM A - Anastrozole; ARM B - Anastrozole + ATRA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent
• Histologically confirmed non-metastatic operable primary invasive HR-positive breast cancer subjected to diagnostic core biopsy
• Menopausal status
• HR-positive/HER2-negative eBC defined as
• ER\>1% on immunohistochemistry (IHC) staining
• HER2 score equal to 0, 1+, 2+ (if FISH neg) on IHC staining
• Available paraffin-embedded tumor block (FFPE) taken at diagnostic biopsy for Ki67 determination (IHC)
• Adequate bone marrow, hepatic and renal function including the following:
• Hb ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L
• Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome
• AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit (or 5x UNL in the presence of liver metastases)
• Creatinine ≤ 1.5 x upper normal limit
• Age ≥ 18 years
• Performance status (PS) ≤ 1 (ECOG scale)

You may not qualify if:

• Presence of metastatic disease
• Pre-menopausal status
• Previous investigational treatment for any condition within 4 weeks of randomization date
• Treatment including radiation therapy, chemotherapy, biotherapy and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry
• Co-existing active infection or serious concurrent illness
• Any medical or other condition that in the Investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
• Gastrointestinal disorders that may interfere with absorption of the study drug.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (2)

Ospedale Santa Maria della Misericordia di Udine

Udine, UD, 33100, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

MeSH Terms

Interventions

Tretinoin; Anastrozole

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: October 3, 2019
• Study Start: June 18, 2019
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)