Conditions: Osteosarcoma
Keywords: Metastatic and/or Recurrent Osteosarcoma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 8
Healthy volunteers: no

Brief summary:
This is a Bayesian designed multi-arm, multi-centre, open label phase II study. The target sample size of 40 patients will be recruited from up to 8 EU countries, but this may be revised in light of the interim analysis. Patients with relapsed or metastatic osteosarcoma will be divided into three treatment groups. They will all either have surgery or a biopsy before and after six weeks exposure to either Mifamurtide alone, Ifosfamide alone, or Mifamurtide combined with Ifosfamide. They will then receive further treatment to a maximum of 42 or 36 weeks in total (depending on Arm), with all patients being able to receive 36 weeks of Mifamurtide treatment.

Detailed description:
Osteosarcoma (OS) is the most common primary tumour arising from bones. There is currently no approved treatment other than surgery for metastatic or recurrent osteosarcoma refractory to chemotherapy. Patients deemed unresectable normally receive chemotherapy prior to attempted resection. The addition of chemotherapy to surgery for metastatic or recurrent osteosarcoma may improve response rates. MEPACT (Mifamurtide, MTP-PE) is licensed for use in the adjuvant osteosarcoma setting; indicated in children, adolescents and young adults for the treatment of high-grade resectable non-metastatic osteosarcoma after macroscopically complete surgical resection. It is used in combination with post-operative multi-agent chemotherapy. This is a Bayesian designed multi-arm, multi-centre open-label phase II study in patients with metastatic and/or recurrent osteosarcoma, which will investigate why some patients with osteosarcoma may respond better than others to mifamurtide given alone or in combination with ifosfamide. Patients with relapsed or metastatic osteosarcoma will be divided into three treatment groups (Arms). Depending on their current disease status, patients may be either Registered to Arm A (resectable group), to receive Mifamurtide alone; or Randomised to Arm B/C (non-resectable group), to receive mifamurtide in combination with ifosfamide. Arm A - Mifamurtide alone; Arm B - Ifosfamide alone for 6 weeks then Ifosfamide + mifamurtide for 6 weeks, then mifamurtide alone for 30 weeks; Arm C - Ifosfamide + mifamurtide for 12 weeks then mifamurtide alone for 24 weeks. All participants will receive 36 weeks or more of mifamurtide. Biopsies (or resected tumour samples) will be obtained before and after 6 weeks of therapy interval in order to determine the pharmacodynamic endpoints. The target sample size is 40 patients. An interim analysis will be performed for the primary efficacy endpoint.

Arms:
arm 1: Treatment Weeks 1-6 (post 1st biopsy/resection):

Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks.

Treatment Weeks 7-12 (post 2nd biopsy/resection):

Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks.

Treatment Weeks 13-36:

Mifamurtide 2mg/m2, IV infusion, once/week. arm 2: Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle).

Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6.

Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. arm 3: Treatment Weeks 1-6:

Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle).

Plus Mifamurtide 2mg/m2, IV infusion, twice per week, each given at least 3 days apart, for 6 weeks.

Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6.

Treatment Weeks 7-12 (post 2nd biopsy/resection):

Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle).

Plus Mifamurtide 2mg/m2, IV infusion, twice per week, given at least 3 days apart, for 6 weeks. Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6.

Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week.

Interventions: intervention 1: Mifamurtide intervention 2: Ifosfamide
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: