Metformin as Maintenance Therapy in Patients With Bone Sarcoma and High Risk of Relapse

NCT04758000 | Recruiting Phase 2

• 2 other identifiers: 794/2020/Farm/IOR2020-002579-37
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Primitive bone sarcoma are rare tumors with low options of therapy for patient treatment.

1. 1.OSTEOSARCOMA VERY POOR RESPONDER COHORT. Necrosis on primitive localized osteosarcoma represents one of the principal prognostic factors. Nowadays, for localized osteosarcoma there is no maintenance therapy that have shown to be effective.
2. 2.OSTEOSARCOMA AND EWING'S SARCOMA AFTER FIRST RELAPSE Maintenance therapy after Complete Remission occurring after Ewing's sarcoma or osteosarcoma patients is not a standard rule.

Conditions

Osteosarcoma; Ewing Sarcoma

Keywords

Metformin; poor responders osteosarcoma; post relapse bone sarcoma

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  Evaluate the event free survival (EFS) in osteosarcoma and Ewing sarcoma patients with high risk of relapse compared to the historical control

  3 years

Secondary Outcomes (1)

• Metformin toxicity

  3 years

Study Arms (1)

Metformin

EXPERIMENTAL

Metformin will be administrated according with patients body mass index (BMI). The study is divided into 2 groups. * Group 1: Localized osteosarcoma that have presented a response ≤ 60% to the pre-operatory chemotherapy). * Group 2: Osteosarcoma and Ewing sarcoma patients with complete remission after the first relapse.

Drug: Metformin Hydrochloride

Interventions

Metformin Hydrochloride DRUG

Metformin will be administrated according with patients body mass index (BMI). Patients between 14 and 18 years old or with BMI ≤ 20: 500 mg two times a day Patients older than 18 years or with BMI \> 20: 850 mg two times a day. In all cases, metformin will be administrated for 3 years maximum, unless there is a progression disease or if toxicity is verified.

Metformin

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Non metastatic osteosarcoma patients with necrosis ≤ 60 % in the end of post-operatory chemotherapy treatment (within 45 days.from the end of chemotherapy treatment).
• Osteosarcoma or Ewing sarcoma patients free from the disease after first relapse (within 45 days.from the local surgery or 45 days from the end of chemotherapy treatment).
• ≥ 14 years.
• Patient should not be participating in other clinical study.
• Patients should be able to swallow.
• Screening up to 30 days from the end of chemotherapy treatment or relapse.
• Start therapy up to 30 days from the screening.
• Normal renal function (creatinine \<1,3 mg/L, clearance creatinine ≥ 70 ml/min) end liver function (total serum bilirubina \<1,2 mg/dL, except Gilbert syndrome patients), AST e ALT \<1,8 times the normal range value

You may not qualify if:

• Type B diabetic patient
• Metastatic patients
• Patients with acute metabolic acidosis (lactic acidosis, diabetic ketoacidosis).
• Patients with renal insufficiency (GFR \< 70 ml/min).
• Patients with acute conditions that could cause kidney alterations as dehydration, severe infection and shock.
• Patients with hepatic insufficiency as acute alcohol intoxication and alcoholism.
• Patients with medical conditions that could cause tissue hypoxia: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
• Pregnant and breastfeeding patients, or young women at childbearing age who cannot exclude the state of pregnancy (possibly excluded by serum pregnancy test (BhCG test), in accordance with the recommendations of the CTFG.

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead

Study Sites (1)

Chemotherapy Div, Istituto Ortopedico Rizzoli

Bologna, Italy

RECRUITING

Related Publications (5)

• Ferrari S, Bacci G, Picci P, Mercuri M, Briccoli A, Pinto D, Gasbarrini A, Tienghi A, Brach del Prever A. Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol. 1997 Aug;8(8):765-71. doi: 10.1023/a:1008221713505.

  PMID: 9332684 BACKGROUND

• Leary SE, Wozniak AW, Billups CA, Wu J, McPherson V, Neel MD, Rao BN, Daw NC. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience. Cancer. 2013 Jul 15;119(14):2645-53. doi: 10.1002/cncr.28111. Epub 2013 Apr 26.

  PMID: 23625626 BACKGROUND

• Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing's sarcoma family of tumors. J Clin Oncol. 2005 Jul 1;23(19):4354-62. doi: 10.1200/JCO.2005.05.105. Epub 2005 Mar 21.

  PMID: 15781881 BACKGROUND

• Ferrari S, Luksch R, Hall KS, Fagioli F, Prete A, Tamburini A, Tienghi A, DiGirolamo S, Paioli A, Abate ME, Podda M, Cammelli S, Eriksson M, Brach del Prever A. Post-relapse survival in patients with Ewing sarcoma. Pediatr Blood Cancer. 2015 Jun;62(6):994-9. doi: 10.1002/pbc.25388. Epub 2015 Jan 13.

  PMID: 25585917 BACKGROUND

• Tsuda Y, Tsoi K, Parry MC, Stevenson JD, Fujiwara T, Sumathi V, Jeys LM. Impact of chemotherapy-induced necrosis on event-free and overall survival after preoperative MAP chemotherapy in patients with primary high-grade localized osteosarcoma. Bone Joint J. 2020 Jun;102-B(6):795-803. doi: 10.1302/0301-620X.102B6.BJJ-2019-1307.R1.

  PMID: 32475245 BACKGROUND

MeSH Terms

Conditions

Osteosarcoma; Sarcoma, Ewing

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Alessandra Longhi, MD

  Istituto Ortopedico Rizzoli IRCSS, Bologna, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandra Longhi, MD

CONTACT

+39(051)6366668; alessandra.longhi@ior.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Model Details: 1. Group 1 Localized osteosarcoma that have presented a response ≤ 60% to the pre-operatory chemotherapy. Is expected the enrolment of 37 patients as total population, in 44 months. The patients will be followed for 3 years, started from the date of enrolment. Metformin will be administrated for 3 years maximum, unless there is a progression disease or if toxicity is verified. 2. Group 2 Osteosarcoma and Ewing sarcoma patients with complete remission after the first relapse. Is expected the enrolment of 30 patients as total population, in 24 months. Metformin will be administrated at the Group 2 for 1 year. If there is no toxicity verified or relapse, the patient should continue the treatment for other 2 year (in a total 3 years as maximum).

Study Record Dates

• First Submitted: February 14, 2021
• First Posted: February 17, 2021
• Study Start: March 1, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 4, 2023

Record last verified: 2023-08

Locations

IT (1)