Evaluating ATRA with Anastrozole for Early Breast Cancer Treatment

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)

This study is testing if adding a medication called ATRA to anastrozole can help shrink early breast cancer in postmenopausal women before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Mario Negri Institute for Pharmacological Research (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Udine, UD and 1 other locations)
• Trial ID: NCT04113863 on ClinicalTrials.gov

What this trial studies

This is a randomized, phase II clinical trial conducted in Italy that investigates the effectiveness of all-trans retinoic acid (ATRA) in combination with anastrozole for treating operable early breast cancer in postmenopausal women. The study aims to assess the anti-tumor activity of this combination therapy during a preoperative 'window-of-opportunity' phase, where patients will receive treatment for four weeks prior to surgery. Participants will be randomized to receive either the combination treatment or anastrozole alone, with the goal of determining if ATRA enhances tumor regression in specific subtypes of hormone receptor-positive, HER2-negative breast cancer.

Who should consider this trial

Good fit: Ideal candidates for this study are postmenopausal women with histologically confirmed, non-metastatic, operable primary invasive hormone receptor-positive breast cancer.

Not a fit: Patients with metastatic breast cancer or those who do not meet the hormonal receptor status criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new therapeutic option that enhances tumor regression in early breast cancer patients.

How similar studies have performed: While ATRA has established efficacy in hematological malignancies, its application in solid tumors like breast cancer is less explored, making this approach relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Signed, informed consent
2. Histologically confirmed non-metastatic operable primary invasive HR-positive breast cancer subjected to diagnostic core biopsy
3. Menopausal status
4. 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
5. Available paraffin-embedded tumor block (FFPE) taken at diagnostic biopsy for Ki67 determination (IHC)
6. Adequate bone marrow, hepatic and renal function including the following:

   1. Hb ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L
   2. Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome
   3. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit (or 5x UNL in the presence of liver metastases)
   4. Creatinine ≤ 1.5 x upper normal limit
7. Age ≥ 18 years
8. Performance status (PS) ≤ 1 (ECOG scale)

Exclusion Criteria:

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

Where this trial is running

Udine, UD and 1 other locations

• Ospedale Santa Maria della Misericordia di Udine — Udine, Ud, Italy (Recruiting)
• ASST Papa Giovanni XXIII — Bergamo, Italy (Recruiting)

Study contacts

• Study coordinator: Vittoria Fotia, MD

Conditions Breast Neoplasm Female