Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Patients With Brain Metastases

NCT04001725 | Unknown Phase 2

• 3 other identifiers: INT31/19B43C170003500012019-000105-73
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This is a monocentric, open label, randomized Phase II study in patients with brain metastasis from melanoma, lung or breast cancer, who require treatment with high-dose dexamethasone, as defined as a minimum of 8 mg daily based on the clinician judgment, for at least three weeks, with or without radiation therapy. The aim is to investigate the metformin efficacy in preventing the onset of glucocorticoid-induced diabetes and other metabolic perturbations in patients with brain metastases from melanoma, lung or breast cancer.

Conditions

Brain Metastases; Melanoma; Lung Cancer; Breast Cancer

Keywords

Metformin; Dexamethasone; Diabetes; Glucocorticoids; Phase II; Tumor; Immune system; Immunological Effects; Metabolic Effects; Anticancer Effects; Randomization; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Metformin in preventing precocious (14 days) dexamethasone-induced diabetes

  To evaluate the efficacy of metformin in preventing precocious (14 days) dexamethasone-induced diabetes, as defined as fasting plasma glucose levels ≥ 126 mg/dl, in patients with brain metastases from melanoma, lung or breast cancer.

  14 days

Secondary Outcomes (14)

• Dexamethasone-induced diabetes at 30 days

  30 days

• Short-term mortality

  90 days

• Brain local control rate of disease

  30 days

• Patient ECOG performance status (PS)

  30 days

• Patient Quality of Life (QoL)

  30 days

Study Arms (2)

A (Dexamethasone)

ACTIVE COMPARATOR

Patients subjected at a minimum daily dosage of 8 mg through the oral, intramuscular or intravenous administration route (control arm). The total dose can either administered once a day or through a refracted schedule

Drug: Dexamethasone

B (Dexamethasone and Metformin)

EXPERIMENTAL

Patients subjected at a minimum daily dosage of 8 mg through the oral, intramuscular or intravenous administration route.The total dose can either administered once a day or through a refracted schedule. The same patients subjected at a metformin. Metformin initial dosage will be 850 mg per day, and will be escalated based on patient tolerability up to a maximum of 2550 mg daily (experimental arm).

Drug: Dexamethasone; Drug: Metformin

Interventions

Dexamethasone DRUG

A minimum daily dosage of 8 mg through the oral, intramuscular or intravenous administration route, once or twice a day.

A (Dexamethasone); B (Dexamethasone and Metformin)

Metformin DRUG

A minimum daily dosage of Dexamethasone 8 mg through the oral, intramuscular or intravenous administration route, once or twice a day and 2550 mg daily (maximum dose), oral administration (OS) of Metformin; starting dose will be 850 mg/day, to be progressively increased to 1700 mg/day on day 4 and 2550 mg/day on day 7, if well tolerated.

Also known as: METFORAL

B (Dexamethasone and Metformin)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 75 years
• Histologically confirmed diagnosis of melanoma, lung (SCLC or NSCLC) or breast cancer
• Recent (28 days), radiologically documented (contrast-enhanced CT or MRI) diagnosis of measurable brain metastases requiring treatment with high-dose dexamethasone (at least 8 mg daily for at least 21 days) plus/minus radiation therapy (RT).
• Any previous or ongoing antitumor systemic therapy; patients who have never received previous systemic therapy can be also included.
• Fasting glycemia \< 126 mg/dl at the baseline evaluation or random glycemia of less than 200 mg/dl if the patient has not fasted for at least 8 hours before blood sampling.
• Adequate blood tests:
• Hemoglobin ≥ 9 g/dl
• Absolute neutrophil count (ANC) in the range between 1.5-10 x 103/μl
• Total bilirubin ≤ 1.5 times the upper normal limit (UNL). For patients with Gilbert syndrome or known liver metastases, bilirubin levels ≤ 3 times the UNL are considered acceptable
• AST, ALT ≤ 3 times the UNL
• Alkaline phosphatase ≤ 2.5 times the UNL
• Serum creatinine concentration ≤ 1.5 x UNL
• ECOG Performance Status ≤ 2
• Life expectancy \> 6 weeks
• Written informed consent

You may not qualify if:

• Leptomeningeal carcinomatosis, either radiologically documented or cytologically confirmed
• History of brain metastases
• Diagnosis of other malignancies in the last 5 years, except for superficial, radically treated basal cell carcinomas of the skin or in situ carcinomas of the cervix
• Previous or current use of metformin
• Ongoing therapy with systemic glucocorticoids at a dosage that is higher than 10 mg prednisone equivalent. Previous GC treatment is allowed if stopped at least 2 months before enrollment. Inhaled or topical steroids are permitted.
• Diagnosis of Type 1 or Type 2 diabetes mellitus
• Known history of HBV- or HCV-related infection
• Known liver cirrhosis, even in the absence of significant alterations in blood tests
• Clinically uncontrolled disorders of the lung, kidney, liver or cardio-vascular apparatus
• Known history of HIV infection
• Serious neurological or psychiatric disorders
• Absence of a caregiver for patients with an ECOG performance status of 2
• Pregnancy or lactation
• Body mass index \< 18.5 kg/m2
• Past or current alcohol abuse (\> 36 grams/day for men and 24grams/day for women)

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• University of Milan: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

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MeSH Terms

Conditions

Brain Neoplasms; Melanoma; Lung Neoplasms; Breast Neoplasms; Diabetes Mellitus; Neoplasms

Interventions

Dexamethasone; Metformin

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Filippo De Braud, Professor

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo De Braud, Professor

CONTACT

0039 02 23902148; Filippo.DeBraud@istitutotumori.mi.it

Claudio Vernieri, MD

CONTACT

0039 02 23903066; Claudio.Vernieri@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Eligible patients will be randomized in a 1:1 ratio. Randomization will be stratified by means of minimization technique according to the following factors: primary tumor (melanoma versus lung versus breast cancer), dexamethasone dosage (8-12 mg vs \>12 mg daily), baseline (pre-enrollment) fasting glycemia (\< 100 versus 100-125 mg/dl). Patients randomized to the experimental arm will discontinue metformin after 30 days, unless diabetes has developed in the meanwhile and the physician believes that metformin is still required for its management. Patients randomized to the control arm who develop steroid-induced diabetes will be prescribed metformin, unless contraindicated, as the preferred therapy option for the management of hyperglycemia. In both treatment arms, dexamethasone will be administered until necessary and at the required dosage in the judgment of the treating physician.

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 28, 2019
• Study Start: October 15, 2019
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: November 13, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)