NCT02488564: met-HEReMYTA

Clinical and Translational Phase II Study of Liposomal Doxorubicin Plus Docetaxel and Trastuzumab with Metformin As Primary Systemic Therapy for Operable and Locally Advanced Recombinant Human ErbB-2 (HER2) Positive Breast Cancer

Completed Phase 2 Last updated 30 January 2025

What this trial tests

Phase 2 trial testing Liposomal doxorubicin in HER-2 Positive Breast Cancer in 49 participants. Completed in 17 March 2020.

Timeline

17 December 2014

Primary endpoint
1 October 2018

17 March 2020

Quick facts

Lead sponsor	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	49
Start date	17 December 2014
Primary completion	1 October 2018
Estimated completion	17 March 2020
Sites	9 locations across Italy

Drugs / interventions tested

• Liposomal doxorubicin (liposomal-doxorubicin) — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →
• Trastuzumab (trastuzumab) — full drug profile →
• Metformin (metformin) — full drug profile →

Conditions studied

• HER-2 Positive Breast Cancer — all drugs for HER-2 Positive Breast Cancer →

Sponsor

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS — full company profile →

Who can join

Adults 18 to 75, any sex, with HER-2 Positive Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Pathologic complete response rate(pCR)
  Time frame: up to 36 months
  Complete pathologic response will be defined as no invasive residuals in breast and axillary nodes. In situ tumor residuals are considered as complete response rate

Sponsor's own description

It is a multicenter, open-label, two stage phase II trial, to assess activity, safety and potential early predictors of response in neoadjuvant setting. Patients with operable breast cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer (T4a-d, N0-N2, M0) with overexpression or amplification of HER2 (AJCC 7th edition 2010) are included in the study.

The primary objective is to evaluate the pathological complete response rate (pCR).

The secondary objectives are:

* to evaluate the clinical response rate (RR).
* to evaluate the feasibility and systemic tolerance, with particular attention to cardiac toxicity.
* to evaluate the conservative surgery rate.

Total duration of the trial is 36 months; planned treatment are 6 cycles of chemotherapy. At every cycle (every 21 days) will be administered:

Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

Publications & conference data

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

1. Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality.
   Ramteke P, Deb A, Shepal V, Bhat MK. · · 2019 · cited 107× · PMID 31546918 · DOI 10.3390/cancers11091402
2. New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.
   Hsu SK, Cheng KC, Mgbeahuruike MO, Lin YH, et al · · 2021 · cited 56× · PMID 34502359 · DOI 10.3390/ijms22179453
3. RETRACTED: Metformin and Breast Cancer: Where Are We Now?
   Cejuela M, Martin-Castillo B, Menendez JA, Pernas S. · · 2022 · cited 55× · PMID 35269852 · DOI 10.3390/ijms23052705
4. Therapeutic Repurposing of Biguanides in Cancer.
   Zhao H, Swanson KD, Zheng B. · · 2021 · cited 47× · PMID 33865798 · DOI 10.1016/j.trecan.2021.03.001
5. Hyperglycemia and Chemoresistance in Breast Cancer: From Cellular Mechanisms to Treatment Response.
   Qiu J, Zheng Q, Meng X. · · 2021 · cited 43× · PMID 33718202 · DOI 10.3389/fonc.2021.628359
6. Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.
   Corleto KA, Strandmo JL, Giles ED. · · 2024 · cited 23× · PMID 38543182 · DOI 10.3390/ph17030396
7. Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer.
   Rocca A, Cortesi P, Cortesi L, Gianni L, et al · · 2021 · cited 17× · PMID 33613693 · DOI 10.1177/1758835920985632
8. Exploratory Analysis of ¹⁸F-3'-deoxy-3'-fluorothymidine (¹⁸F-FLT) PET/CT-Based Radiomics for the Early Evaluation of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer.
   Fantini L, Belli ML, Azzali I, Loi E, et al · · 2021 · cited 12× · PMID 34249671 · DOI 10.3389/fonc.2021.601053