Exploiting metformin plus/minus cyclic FAsting Mimicking diet (FMD) to improve the Efficacy of platinum-pemetrexed chemotherapy in advanced LKB1-mutated lung adenocarcinoma: the FAME trial

Phase 1

• Conditions: Patients with LKB1-mutated advanced lung adenocarcinomas; MedDRA version: 21.0Level: PTClassification code 10025038Term: Lung adenocarcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10025037Term: Lung adenocarcinoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000788-95-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1.Age included between 18 and 75 years.
2.Histologically confirmed diagnosis of LKB1-mutated lung adenocarcinoma.
3.Absence of EGFR mutations, ALK and ROS-1 rearrangements, high expression of PD-L1 (= 50% in immunoistochemistry).
4.Advanced disease, defined as unresectable, locally advanced (stage IIIB) or metastatic (stage IV), not candidate to concomitant or sequential definitive chemo-radiation.
5.Signed and dated informed consent, indicating that the patient has been informed on all the aspects of the study prior to the enrollment.
6.Patient’s will and capability to respect the protocol recommendations as regards FMD, laboratory tests and other procedures.
7.Eastern Cooperative Oncology Group (ECOG) performance status 0 o 1.
8.In case of presence of brain metastases, absence of neurologic symptoms, need for radiotherapy and steroid therapy at a dose = 25 mg per day of prednisone or analogues.
9.Adequate bone marrow and organ function
10.Fasting plasma glucose concentration = 200 mg/dL.
11.For women of childbearing potential, consent to maintain abstinence from sexual intercourse or to use highly effective contraceptive methods (that is, with a failure rate < 1% per year) for the whole duration of the study and for almost 30 days after the conclusion of the FMD. Abstinence is acceptable only if in line with the patient’s lifestyle. Adequate contraceptive methods include tube ligation, male sterilization, hormone implants, injectable or oral hormone contraceptives and some intra-uterine devices. Alternatively, two different contraceptive methods must be combined (e.g. two barrier methods like condom and cervical cap) in order to obtain a failure rate <1% per year. Barrier methods must always be associated to a sperm killer.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

1.Previous systemic therapies for advanced lung cancer.
2.Evidence of disease relapse within 6 months from the conclusion of adjuvant or neoadjuvant platinum-based chemotherapy.
3.Diagnosis of other malignancies in the previous 5 years, except for adequately treated basal or squamous skin cancer or radically excised cervical cancers. Other malignancies diagnosed more than 5 years before the diagnosis of lung cancer must have been radically treated without evidence of relapse.
4.Body mass index (BMI) < 20 kg/m2.
5.Anamnesis of alcohol abuse.
6.Non-intentional weight loss = 5% in the previous 3 months, unless the patient has a BMI > 25 kg/ m2 at the time of enrollment in the study, or non-intentional weight loss of = 10% in the previous 3 months, unless the patients has a BMI > 22 kg/m2 at the time of the enrollment in the study. In both cases, weight must be stable for at least one month.
7.Active pregnancy or breast feeding.
8.Active B or C hepatitis.
9.Serious infection in the previous 4 weeks before the start of FMD, including, but not limited to, potential hospitalizations for complications of infections, bacteriemia or serious pneumonitis.
10.Active autoimmune diseases requiring systemic treatments (e.g. systemic steroids or immune suppressants).
11.Recent diagnosis of hypothyroidism requiring systemic substitutive hormonal therapy and without stabilization of hormonal profile (fT3, fT4 and TSH within the normal range).
12.Diagnosis of type 1 or 2 diabetes mellitus or requiring pharmacologic therapy (including, but not limited to, insulin, secretagogues and metformin).
13.Serious impair of gastrointestinal function or gastrointestinal disease potentially altering nutrient digestion or absorption during re-alimentation phase (e.g. active gastric or intestinal ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small intestine resection).
14.Anamnesis of human immunodeficiency virus (HIV).
15.Anamnesis of clinically significant heart disease including:
-angina pectoris, coronary bypass, symptomatic pericarditis, myocardial infarction in the previous 12 months from the beginning of experimental therapy;
-congestive heart failure (NYHA III-IV).
16.Anamnesis of cardiac arrhythmias (e.g. ventricular tachycardia, chronic atrial fibrillation, complete bundle branch block, high grade atrio-ventricular block like bi-fascicular block, type II Mobitz and third grade atrio-ventricular block, nodal arrhythmias, supra-ventricular arrhythmias) or conduction abnormalities in the previous 12 months from the beginning of experimental therapy.
17.Reduction in left ventricular ejection fraction to < 50% at the cardiac scan with radionuclides or at echocardiography.
18.Previous episodes of symptomatic hypotension leading to loss of consciousness.
19.Plasma fasting glucose = 65 mg/dL.
20.Active therapy with systemic steroids at a dose = 25 mg per day of prednisone or equivalent.
21.Medical or psychiatric comorbidities rendering the patient not candidate to the clinical trial, according to the investigator’s judgement.
22.pO2 < 70 mmHg, lactates above normal limits and pH value below normal limits at arterial hemogasanalysis.
23.Need for chronic oxygen therapy.
24.Other cardiac, liver, lung or renal comorbidities, not specified in the previous inclusion or exclusion criteria, but potentially exposing the patient to a high risk of lactic acidosis.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified