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Metformin Plus/Minus Fasting Mimicking Diet to Target the Metabolic Vulnerabilities of LKB1-inactive Lung Adenocarcinoma

NCT03709147 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 64

Last updated 2020-11-16

No results posted yet for this study

Summary

Lung adenocarcinoma with inactive LKB1 has emerged as a particularly aggressive form of lung cancer, with poor response to immune checkpoint inhibitors. Recent preclinical evidences have demonstrated that LKB1-inactive lung adenocarcinoma is characterized by specific metabolic vulnerabilities, which make it hypersensitive to energetic crisis. For instance, by inhibiting mitochondrial metabolism and reducing ATP availability to cancer cells, the antidiabetic compound metformin has anticancer activity and prevents acquired resistance to cisplatin in lung adenocarcinoma with inactive LKB1. Similarly to metformin, glucose starvation, which can be recapitulated in vivo by cyclic fasting or fasting-mimicking diet (FMD), can cause metabolic crisis in these neoplasms. In this trial, the investigators will assess for the first time the efficacy of combining standard-of-care platinum-based chemoimmunotherapy with metformin plus/minus FMD in patients with LKB1-inactive, advanced lung adenocarcinoma.

Conditions

  • Advanced LKB1-inactive Lung Adenocarcinoma

Interventions

DRUG

Metformin Hydrochloride

Metformin 1500 mg/day up to disease progression or unacceptable toxicity Every-21-days, 5-day Fasting-mimicking diet (FMD)

DRUG

Cisplatin

Intravenous cisplatin, administered at a dosage of 75 mg/mq every three weeks for a maximim of 4 consecutive cycles

DRUG

Carboplatin

Carboplatin at an area-under-the-curve (AUC) of 5, administered intravenously every-three weeks for a maximum of 4 consecutive cycles

DRUG

Pemetrexed

Pemetrexed, administered intravenously at the dose of 500 mg/mq every-three weeks up to a maximum of 4 cycles in combination with platinum compounds, and then as a maintenance treatments in patients not undergoing disease progression after the first 4 chemotherapy cycles

DIETARY_SUPPLEMENT

Fasting-mimicking diet

5-day fasting-mimicking diet regimen, consisting of 700 KCal on day 1, 300 KCal on days 2-4, and 450 KCal on day 5, to be repeated every three weeks up to a maximum of 4 cycles

DRUG

Pembrolizumab

Pembrolizumab, administered intravenously at the flat dose of 200 mg every-three weeks up to a maximum of 4 cycles in combination with platinum compounds, and then as a maintenance treatments in patients not undergoing disease progression after the first 4 chemotherapy cycles

Sponsors & Collaborators

  • Marina Garassino

    lead OTHER

Principal Investigators

  • Marina Chiara Garassino, M.D. · Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-10-30
Primary Completion
2023-09-10
Completion
2023-09-10

Countries

  • Italy

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03709147 on ClinicalTrials.gov