Topic: Cancer
Conditions
Interventions
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
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)
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Relapsed osteosarcoma (first, second, third or any relapse, patient has recovered from chemotherapy and any other investigational drug/agent treatment, radiotherapy or surgical procedure). 2. Histological confirmed diagnosis of osteosarcoma at original presentation. 3. Tumour at biopsy accessible or resectable site. 4. Progressive disease documented by imaging within 3 months of entry into the trial. 5. At least one measurable lesion on CT scan (RECIST) performed in past 21 days prior to trial entry. 6. Male or female, age = 16 years to 65 (or =18 based on institutional practice for Teenage and Young Adult Cancer patients). 7. Life expectancy of at least 3 months. 8. WHO performance score of 0 - 2. 9. The patient is willing and able to comply with the protocol and scheduled follow-up visits and examinations. 10. Written (signed and dated) informed consent. 11. Cardiac shortening fraction = 28% or ejection fraction = 45% 12. Renal function is adequate for ifosfamide treatment (GFR as per table below, other renal function screening tests as per local practice) 13. Haematological and biochemical indices within the ranges detailed in the protocol
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding woman. Men or women of childbearing potential unless effective methods of contraception are used during study treatment and for at least 7 days after the last mifamurtide dose. 2. 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. 3. Contraindications to lung biopsies 4. Hypersensitivity to ifosfamide or any component of the formulation. 5. Previously diagnosed brain metastases. 6. Significant active cardiac disease including: uncontrolled high blood pressure (no greater than 2 standard deviations above the mean for age for systolic blood pressure (SBP) and diastolic blood pressure (DBP), unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias and with a history of pericarditis and myocarditis 7. Treatment with any other investigational agent, or participation in another interventional clinical trial within 21 days prior to enrolment. 8. Major surgery within 21 days prior first study biopsy 9. Currently taking of high-dose nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroid treatment 10. Concurrent use of ciclosporin or other calcineurin inhibitors. 11. Any psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results. 12. Any other active malignancy, with the exception of adequately treated conebiopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions. 13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. * mifamurtide-like drugs include GMCSF, interferon and other macrophage activating molecules.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Radiological response; Timepoint(s): Pre-treatment, after 6, 12, 18, 24 & 36 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Biological response; Timepoint(s): Pre-treatment and after 6 weeks of treatment 2. Disease specific overall survival; Timepoint(s): End of trial 3. Progression free survival on serial CT scan; Timepoint(s): Pre-treatment, after 6, 12, 18, 24 and 36 of weeks of treatment 4. Safety and tolerability on CTCAE Criteria (v4.0); Timepoint(s): Throughout trial treatment | — |
Countries
United Kingdom
Outcome results
None listed