NCT04248998

Calorie Restriction With or Without Metformin in Triple Negative Breast Cancer

Targeting Triple Negative BREAst Cancer Metabolism With a Combination of Chemotherapy and a Diet Mimicking FASTing Plus/Minus Metformin in the Preoperative Setting: the BREAKFAST Trial

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Glucose starvation and metformin have synergistic antitumor effects that are mediated through the concomitant inhibition of glycolysis and mitochondrial oxidative phosphorylation. The BREAKFAST trial will evaluate the antitumor activity of combining cyclic fasting-mimicking diet (FMD), which reproduces the in vitro effects of glucose starvation, plus/minus metformin with standard preperative anthracycline-taxane chemotherapy in patients with stage I-III TNBC

Detailed description

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and is associated with the lowest cure rates in the limited-stage disease setting, as well as with the lowest overall survival in the metastatic setting. Preclinical studies indicate that cycles of fasting or calorie-restricted, low-carbohydrate, low-protein diets, also known as fasting-mimicking diets (FMDs), have synergistic cytotoxic effects when combined with chemotherapy agents, such as doxorubicin or cisplatin, in several in vitro and in vivo tumor models, including murine TNBC models. More recently, intermittent fasting has demonstrated highly synergistic antitumor effects when combined with metformin; of note, these effects are mediated through the concomitant inhibition of glycolysis (via fasting-induced hypoglycemia) and metformin-induced inhibition of mitochondrial oxidative phosphorylation (OXPHOS). Finally, small reports published so far indicate that cyclic fasting and FMDs are well tolerated in cancer patients, and can be safety combined with standard antitumor treatments. Based on these data, the BREAKFAST trial was designed to investigate the antitumor activity of cyclic FMD, alone or in combination with metformin, in patients with localized TNBC. In this study, 90 patients with stage I-III TNBC will be randomized in a 1:1 ratio to receive approximately 6 months of standard preoperative anthracycline plus taxane chemotherapy in combination with eight triweekly cycles of 5-day FMD (Arm A), or the same chemotherapy-FMD regimen plus daily metformin (Arm B). The primary objective of the study is to demonstrate that one or both experimental treatments increase the rate of pCR from 45% (historical data) to 65%

Conditions

• Triple-negative Breast Cancer

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Fasting-mimicking diet	Cyclic, 5-day, calorie-restricted (600 KCal on day 1; 300 KCal on days 2-5), low-carbohydrate, low protein diet every three weeks
DRUG	Metformin	Metformin 850 mg twice a day
DRUG	Preoperative chemotherapy	Chemotherapy will consist of: * four triweekly cycles of doxorubicin 60 mg/mq plus cyclophosphamide 600 mg/mq, followed by * twelve consecutive cycles of weekly paclitaxel 80 mg/mq

Timeline

• Start date: 2020-05-05
• Primary completion: 2024-05-01
• Completion: 2024-05-01
• First posted: 2020-01-30
• Last updated: 2023-01-18

Locations

1 site across 1 country: Italy