Relapsed or metastatic osteosarcoma MedDRA version: 17.0 Level: PT Classification code 10031291 Term: Osteosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: MEPACT
Product Name: mifamurtide
Product Code: n/a
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Muramyl tripeptide phosphatidyl ethanolamine
CAS Number: 83461
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible for inclusion in this study if all of the following criteria apply. 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 Are the trial subjects under 18? yes Number of subjects for this age range: 8 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Patient will not be eligible for the trial if any of the following apply: 1. Pregnant or breast-feeding 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 non-steroidal anti-inflammatory 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 cone-biopsied 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 |
|---|---|
| Main Objective: The principal research question is to identify markers of response to mifurmatide by looking at biological markers of immune response activation in tumour biopsies taken before and after 6 weeks of treatment. The pharmacodynamic readouts will be compared with radiological (CT scan) response measured by standard RECIST criteria.;Secondary Objective: The study secondary objectives are to: 1) assess the safety and tolerability of mifarmurtide in patients with advanced osteosarcoma when combined with standard surgery and/or chemotherapy; 2) Assess the systemic immune modulating effects of mifarmurtide by measuring cytokine activation before and throughout treatment; 3) determine overall survival 4) determine progression free survival confirmed by cross-sectional imaging (CT scans as above;Primary end point(s): The primary endpoint is to determine the efficacy of mifamurtide treatment according to biological and radiological markers of response. ;Timepoint(s) of evaluation of this end point: Pre-treatment and after 6 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective radiological response (RECIST 1.1) 2) Toxicity including Laboratory abnormalities (grade 3-4)(CTCAE Criteria (v4.0) 3) Biological response based on changes in systemic levels of mifamurtide activated cytokines, markers of acute phase response and circulating DNA 4) Disease specific overall survival 5) Progression free survival on serial CT scan;Timepoint(s) of evaluation of this end point: 1) Throughout trial participation 2) Prior to starting treatment, at week 1, 4, 6, 7 and 3 weekly thereafter during treatment and at the end of treatment visit 3) Pre-treatment, after 6, 12, 24 & 36 of weeks of treatment 4) end of trial (LVLP) 5) Pre-treatment, after 6, 12, 24 & 36 of weeks of treatment | — |
Countries
Germany, Italy, Netherlands
Contacts
Public ContactClinical Trial Coordinator
OCTO, University of Oxford
Outcome results
None listed