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

Sponsor
Istituto Ortopedico Rizzoli
Study ID
NCT04758000
Phase
PHASE2
Status
Recruiting
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Conditions

  • Ewing Sarcoma
  • Osteosarcoma

Eligibility Criteria

Sex
ALL
Age
14 Years - N/A
Healthy Volunteers
Not accepted

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.

Study Details

Primitive bone sarcoma are rare tumors with low options of therapy for patient treatment. 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. In ISG-OS1 study in patients with necrosis \< 60% had an event free survival (EFS) at 3 yrs of 20% (Ferrari S ) in a more recent analysis (Tsuda Y 2020) patients with a necrosis \<60% had a 3 y EFS of 35% . 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. These patients when free from disease, after first relapse, are more likely to face a second relapse. EFS at ONE YEAR after first relapse in osteosarcoma is shown in literature to be around 21% (Leary SE 2013) and 16% (Tirtei E 2017). The EFS at ONE YEAR after first relapse in Ewing's sarcoma is inferior to 20% (Barker 2005, Ferrari S 2015). A maintenance therapy with low toxicity in these high risk patients could be an option. Metformin has been reported to a reduce the incidence of different type of cancer in diabetic patients. Metformin is well tolerated in diabetics an it is used in other conditions in non diabetic, as ovarian polycystic syndrome, metabolic syndrome and obesity. Metformin has been employed as chemoprevention related to its mechanism of action in breast cancer (NCT01101438 ) and in pediatric cancer together with chemotherapy (NCT01528046). This study aim to explore the effectiveness of metformin (a low cost and well tolerated drug) as maintenance therapy in osteosarcoma and Ewing sarcoma patients at high risk of relapse.

Key Dates

Start date
Mar 1, 2021
Status verified
Aug 2023
Primary completion
Jul 31, 2027
Completion
Jul 31, 2027

Study Design

Enrollment
67 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION

Arms

  • Experimental: Metformin
    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.

Primary Outcome Measure

Event Free Survival [ Time Frame: 3 years ]

Central Contacts

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