Sponsor: University of Oxford
Target recruitment: Approx. 40 patients
Recruitment Period: 18 months from November 2014
Patients are allocated to one of three treatment arms
All patients either have surgery or a biopsy before and after six weeks exposure to either mifamurtide alone, Ifosfamide alone, or mifamurtide combined with Ifosfamide. Further treatment to a maximum of 36 or 42 weeks in total, with all patients being able to receive 36 weeks of mifamurtide treatment.
Paired material before and after treatment (mifamurtide alone, Ifosfamide alone or the combination) will be obtained.
Mifamurtide is given as 2 mg/m2, IV infusion, with each infusion given at least 3 days apart; twice per week for 12 consecutive treatment weeks, then once per week until treatment end.
Ifosfamide (Arm B & C only) is given as 12-15 g/m2 IV infusion infused over 4-5 days as per local practice including concurrent dosing with mesna for 12 consecutive treatment weeks
Main Inclusion Criteria*
- Relapsed osteosarcoma (first, second, third or any relapse, patient has recovered from chemotherapy and any other investigational drug/agent treatment, radiotherapy or surgical procedure).
- Histological confirmed diagnosis of osteosarcoma at original presentation.
- Tumour at biopsy accessible or resectable site.
- Progressive disease documented by imaging within 3 months of entry into the trial.
- At least one measurable lesion on CT scan (RECIST) performed in past 21 days prior to trial entry.
- Male or female, age ≥ 16 years to 65 (or ≥18 based on institutional practice for Teenage and Young Adult Cancer patients).
Main Exclusion Criteria*
- Pregnant or breast-feeding woman.
- Previous treatment with mifamurtide or a mifamurtide like drug in a clinical trial setting for the treatment of metastatic and/or recurrent osteosarcoma in the six months prior to registration.
- Contraindications to lung biopsies.
- Hypersensitivity to ifosfamide or any component of the formulation.
- Previously diagnosed brain metastases.
- Significant active cardiac disease.
- Major surgery within 21 days prior to first study biopsy.
- Currently taking high-dose non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroid treatment.
- Concurrent use of ciclosporin or other calcineurin inhibitors.
To determine the efficacy of mifamurtide treatment
Biological and radiological response
* See Protocol for other objectives/endpoints and list of all inclusion/exclusion criteria
IMP Provider: Millennium-Takeda
Funded by: EU FP7 EuroSARC Grant