Brain MetastasesPhase 2OPTIMALNCT04001725
Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Patients With Brain Metastases
A Phase 2 study testing Dexamethasone and Metformin in people with Brain Metastases and Melanoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Brain Metastases, Melanoma, Lung Cancer
- What is being tested?
- Dexamethasone and Metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteItaly
- Study dates
- 15 Oct 2019to 31 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 18Show fewer
- 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
- Ability to swallow metformin tablets
- Patients of female gender with the potential of childbearing (neither surgically sterile nor 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for at least 60 days after study conclusion. Acceptable methods of contraception include double barrier method [i.e. condom and occlusive cap (diaphragm or cervical vault caps)] spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method.
- Patients of male gender having female partners with childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 60 days after participation in the study
Who cannot join
- 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
Show all 17Show fewer
- 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)
- Documented metabolic acidosis from any cause in the last 5 years
- History of allergy or hypersensitivity to study drug components
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Claudio Vernieri, M.D., Ph.D., +39 02 23903066, claudio.vernieri@istitutotumori.mi.it
About this study
Official title: Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Melanoma, breAst or Lung Cancer Patients With Brain Metastases: the Phase II OPTIMAL Study
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.
Read the detailed description
The study will be conducted in approximately 110 adult patients. aim of the study is to evaluate the effect of oral metformin in preventing GC-induced alterations of systemic metabolism, and in particular GC-induced diabetes. Other clinical objectives of the study consist in investigating the impact of metformin on precocious mortality, deterioration of ECOG PS and local (brain) disease control rate at one month. As an exploratory analysis, the effect of dexamethasone plus/minus metformin on other metabolites or growth factors (including amino acids, fatty acids, ketone bodies, IGF-1), as well as on the number, activation status and metabolism of peripheral blood immune cell populations will be evaluated
- Conditions
- Brain Metastases, Melanoma, Lung Cancer, Breast Cancer
- Being tested
- Dexamethasone, Metformin
- Keywords
- Metformin, Dexamethasone, Diabetes, Glucocorticoids, Phase II, Tumor, Immune system, Immunological Effects, Metabolic Effects, Anticancer Effects, Randomization, Quality of Life
- Medical subject headings
- Brain Neoplasms, Melanoma, Lung Neoplasms, Breast Neoplasms, Diabetes Mellitus, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
A minimum daily dosage of 8 mg through the oral, intramuscular or intravenous administration route, once or twice a day.
MetforminDrug
Also called METFORAL
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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). Receives: Drug: Dexamethasone; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days
Secondary outcomes (14)
Dexamethasone-induced diabetes at 30 days
To study the efficacy of metformin in preventing dexamethasone-induced diabetes at 7 and 30 days after dexamethasone initiation, as defined as fasting plasma glucose levels ≥ 126 mg/dl, in patients with brain metastases from melanoma, lung or breast
Measured: 30 days
Short-term mortality
To evaluate the efficacy of metformin in modifying short-term mortality (3 months) in patients taking high-dose dexamethasone
Measured: 90 days
Brain local control rate of disease
To evaluate the efficacy of metformin in modifying the local disease control rate (brain) in patients treated with radiation therapy (RT) plus dexamethasone at 1 month
Measured: 30 days
Patient ECOG performance status (PS)
To test the impact of metformin on precocious modifycation of patient ECOG Performance Status (PS) at 1 month after initiation of dexamethasone therapy.
Measured: 30 days
Patient Quality of Life (QoL)
Patient QoL will be evaluated through the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C-30 version 3.0. The EORTC QLQ.C30 instrument will be scored according to the EORTC guidelines.
Measured: 30 days
Absolute counts of immune cell populations
To investigate the potential impact of metformin on absolute counts of immune cell populations
Measured: 2 years
Relative counts of immune cell populations
To investigate the potential impact of metformin on relative counts and activation status of activated antitumor lymphocytes
Measured: 2 years
Activation status of immune cell populations
To investigate the potential impact of metformin on activated antitumor lymphocytes
Measured: 2 years
Plasma lipids profile
To study the effect of metformin in modifying the plasma lipid profile at 14 days after treatment initiation
Measured: 14 days
Plasma lipids profile
To study the effect of metformin in modifying the plasma lipid profile at 30 days after treatment initiation
Measured: 30 days
Systemic inflammatory parameters
To investigate the effect of metformin on systemic plasma cytokines (G-CSF, GM-CSF, CCL2, VEGFA)
Measured: 2 years
GC-induced changes in gut microbiota populations
To evaluate the impact of high-dose GCs on gut microbiota populations (30 days)
Measured: 30 days
Metformin-induced changes in gut microbiota populations
To evaluate the impact of metformin on gut microbiota populations (30 days)
Measured: 30 days
Amino acid profile
To study the effect of metformin in modifying the plasma amino acid profile at 14 days after treatment initiation
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2019
- Study start15 Oct 2019
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Milan
- Responsible party
- Principal investigator, Filippo de Braud, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Investigators
- Filippo De Braud, Professor, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04001725
- Sponsor's protocol ID
- INT31/19
- Other IDs
- B43C17000350001, 2019-000105-73, 2019
- Acronym
- OPTIMAL
- Status last verified
- Nov 2019
- First submitted
- 4 Jun 2019
- Last updated
- 13 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.
PubMed 21376230Vernieri C, Casola S, Foiani M, Pietrantonio F, de Braud F, Longo V. Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions. Cancer Discov. 2016 Dec;6(12):1315-1333. doi: 10.1158/2159-8290.CD-16-0615. Epub 2016 Nov 21.
PubMed 27872127O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016 Sep;16(9):553-65. doi: 10.1038/nri.2016.70. Epub 2016 Jul 11.
PubMed 27396447Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84. doi: 10.1200/JCO.2015.60.9503. Epub 2015 Aug 17.
PubMed 26282648Harris D, Barts A, Connors J, Dahl M, Elliott T, Kong J, Keane T, Thompson D, Stafford S, Ur E, Sirrs S. Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study. Curr Oncol. 2013 Dec;20(6):e532-8. doi: 10.3747/co.20.1499.
PubMed 24311953Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP, Kantarjian HM, O'Brien SM. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004 Mar 15;100(6):1179-85. doi: 10.1002/cncr.20071.
PubMed 15022284Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003 May;125(5):1007-21. doi: 10.1067/mtc.2003.181.
PubMed 12771873Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Minambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes. 2014 Jan;6(1):9-20. doi: 10.1111/1753-0407.12090. Epub 2013 Oct 29.
PubMed 24103089Oyer DS, Shah A, Bettenhausen S. How to manage steroid diabetes in the patient with cancer. J Support Oncol. 2006 Oct;4(9):479-83. No abstract available.
PubMed 17080737Bozzi F, Mogavero A, Varinelli L, Belfiore A, Manenti G, Caccia C, Volpi CC, Beznoussenko GV, Milione M, Leoni V, Gloghini A, Mironov AA, Leo E, Pilotti S, Pierotti MA, Bongarzone I, Gariboldi M. MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. J Exp Clin Cancer Res. 2017 Jan 23;36(1):16. doi: 10.1186/s13046-016-0475-z.
PubMed 28114961Wallace MD, Metzger NL. Optimizing the Treatment of Steroid-Induced Hyperglycemia. Ann Pharmacother. 2018 Jan;52(1):86-90. doi: 10.1177/1060028017728297. Epub 2017 Aug 24.
PubMed 28836444Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-induced hyperglycemia. Am J Med Sci. 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01.
PubMed 23531958Zhang ZJ, Bi Y, Li S, Zhang Q, Zhao G, Guo Y, Song Q. Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and meta-analysis. Am J Epidemiol. 2014 Jul 1;180(1):11-4. doi: 10.1093/aje/kwu124. Epub 2014 Jun 10.
PubMed 24920786Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010 Jun;33(6):1304-8. doi: 10.2337/dc09-1791. Epub 2010 Mar 18.
PubMed 20299480Pusceddu S, Vernieri C, Di Maio M, Marconcini R, Spada F, Massironi S, Ibrahim T, Brizzi MP, Campana D, Faggiano A, Giuffrida D, Rinzivillo M, Cingarlini S, Aroldi F, Antonuzzo L, Berardi R, Catena L, De Divitiis C, Ermacora P, Perfetti V, Fontana A, Razzore P, Carnaghi C, Davi MV, Cauchi C, Duro M, Ricci S, Fazio N, Cavalcoli F, Bongiovanni A, La Salvia A, Brighi N, Colao A, Puliafito I, Panzuto F, Ortolani S, Zaniboni A, Di Costanzo F, Torniai M, Bajetta E, Tafuto S, Garattini SK, Femia D, Prinzi N, Concas L, Lo Russo G, Milione M, Giacomelli L, Buzzoni R, Delle Fave G, Mazzaferro V, de Braud F. Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. Gastroenterology. 2018 Aug;155(2):479-489.e7. doi: 10.1053/j.gastro.2018.04.010. Epub 2018 Apr 13.
PubMed 29655834
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of metfOrmin in PrevenTIng Glucocorticoid-induced Diabetes in Melanoma, breAst or Lung Cancer Patients With Brain Metastases: the Phase II OPTIMAL Study
- ClinicalTrials.gov ID
- NCT04001725
- Acronym / sponsor ID
- OPTIMAL / INT31/19
- Conditions
- Brain Metastases, Melanoma, Lung Cancer, Breast Cancer
- Keywords
- Metformin, Dexamethasone, Diabetes, Glucocorticoids, Phase II, Tumor, Immune system, Immunological Effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Collaborators
- University of Milan
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 28 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will be conducted in approximately 110 adult patients. aim of the study is to evaluate the effect of oral metformin in preventing GC-induced alterations of systemic metabolism, and in particular GC-induced diabetes. Other clinical objectives of the study consist in investigating the impact of metformin on precocious mortality, deterioration of ECOG PS and local (brain) disease control rate at one month. As an exploratory analysis, the effect of dexamethasone plus/minus metformin on other metabolites or growth factors (including amino acids, fatty acids, ketone bodies, IGF-1), as well as on the number, activation status and metabolism of peripheral blood immune cell populations will be evaluated
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| A (Dexamethasone) | Active comparator | Drug: DexamethasonePatients 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 |
| B (Dexamethasone and Metformin) | Experimental | Drug: Dexamethasone, Drug: MetforminPatients 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneA minimum daily dosage of 8 mg through the oral, intramuscular or intravenous administration route, once or twice a day. | Drug | A (Dexamethasone), B (Dexamethasone and Metformin) |
| MetforminAlso: METFORALA 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. | Drug | B (Dexamethasone and Metformin) |
Primary outcome
Metformin in preventing precocious (14 days) dexamethasone-induced diabetes
Time frame: 14 days
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 secondary outcomes
Dexamethasone-induced diabetes at 30 days
Time frame: 30 days
Short-term mortality
Time frame: 90 days
Brain local control rate of disease
Time frame: 30 days
Patient ECOG performance status (PS)
Time frame: 30 days
Patient Quality of Life (QoL)
Time frame: 30 days
Absolute counts of immune cell populations
Time frame: 2 years
Relative counts of immune cell populations
Time frame: 2 years
Activation status of immune cell populations
Time frame: 2 years
Plasma lipids profile
Time frame: 14 days
Plasma lipids profile
Time frame: 30 days
Systemic inflammatory parameters
Time frame: 2 years
GC-induced changes in gut microbiota populations
Time frame: 30 days
Metformin-induced changes in gut microbiota populations
Time frame: 30 days
Amino acid profile
Time frame: 14 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Background: PubMed 21376230Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.
- Background: PubMed 27872127Vernieri C, Casola S, Foiani M, Pietrantonio F, de Braud F, Longo V. Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions. Cancer Discov. 2016 Dec;6(12):1315-1333. doi: 10.1158/2159-8290.CD-16-0615. Epub 2016 Nov 21.
- Background: PubMed 27396447O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016 Sep;16(9):553-65. doi: 10.1038/nri.2016.70. Epub 2016 Jul 11.
- Background: PubMed 26282648Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84. doi: 10.1200/JCO.2015.60.9503. Epub 2015 Aug 17.
- Background: PubMed 24311953Harris D, Barts A, Connors J, Dahl M, Elliott T, Kong J, Keane T, Thompson D, Stafford S, Ur E, Sirrs S. Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study. Curr Oncol. 2013 Dec;20(6):e532-8. doi: 10.3747/co.20.1499.
- Background: PubMed 15022284Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP, Kantarjian HM, O'Brien SM. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004 Mar 15;100(6):1179-85. doi: 10.1002/cncr.20071.
- Background: PubMed 12771873Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003 May;125(5):1007-21. doi: 10.1067/mtc.2003.181.
- Background: PubMed 24103089Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Minambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes. 2014 Jan;6(1):9-20. doi: 10.1111/1753-0407.12090. Epub 2013 Oct 29.
- Background: PubMed 17080737Oyer DS, Shah A, Bettenhausen S. How to manage steroid diabetes in the patient with cancer. J Support Oncol. 2006 Oct;4(9):479-83. No abstract available.
- Background: PubMed 28114961Bozzi F, Mogavero A, Varinelli L, Belfiore A, Manenti G, Caccia C, Volpi CC, Beznoussenko GV, Milione M, Leoni V, Gloghini A, Mironov AA, Leo E, Pilotti S, Pierotti MA, Bongarzone I, Gariboldi M. MIF/CD74 axis is a target for novel therapies in colon carcinomatosis. J Exp Clin Cancer Res. 2017 Jan 23;36(1):16. doi: 10.1186/s13046-016-0475-z.
- Background: PubMed 28836444Wallace MD, Metzger NL. Optimizing the Treatment of Steroid-Induced Hyperglycemia. Ann Pharmacother. 2018 Jan;52(1):86-90. doi: 10.1177/1060028017728297. Epub 2017 Aug 24.
- Background: PubMed 23531958Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-induced hyperglycemia. Am J Med Sci. 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01.
- Individual participant dataSharing planned: No
Related trials for Brain Metastases
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
Epidural Hydroxyethyl Starch for Post-Dural Puncture Headache in Parturients
Parturients, Accidental Puncture of Dura During Anaesthesia
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 2/3
RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
HER2-positive Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filippo De Braud, Professor principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone and Metformin in people with Brain Metastases and Melanoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Filippo De Braud, Professor (0039 02 23902148, Filippo.DeBraud@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metformin in preventing precocious (14 days) dexamethasone-induced diabetes (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04001725, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.