Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Mr Ade Faleti
ORCID ID
Contact details
Oncology Clinical Trials Office (OCTO) - Department of Oncology
Old Road Campus
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
-
Eurosarc@octo-oxford.org.uk
Additional identifiers
EudraCT number
2012-000615-84
ClinicalTrials.gov number
NCT02441309
Protocol/serial number
16801
Study information
Scientific title
A Mechanistic Study Of Mifamurtide (MTPPE) In Patients With Metastatic And/Or Recurrent Osteosarcoma
Acronym
MEMOS: a Eurosarc Study of Mifamurtide in advanced osteosarcoma
Study hypothesis
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.
Ethics approval
South Central - Oxford C Research Ethics Committee, 13/06/2014, ref: 14/SC/0255
Study design
Both; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Cancer; Subtopic: Sarcoma; Disease: Bone
Intervention
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.
Intervention type
Drug
Phase
Phase II
Drug names
Mifamurtide, Ifosfamide
Primary outcome measure
Objective Radiological response; Timepoint(s): Pre-treatment, after 6, 12, 18, 24 & 36 weeks of treatment
Secondary outcome measures
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
Overall trial start date
12/09/2014
Overall trial end date
11/03/2016
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 40; UK Sample Size: 10
Participant 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.
Recruitment start date
12/09/2014
Recruitment end date
11/03/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Oncology Clinical Trials Office (OCTO)
Oxford
OX3 7DQ
United Kingdom
Funders
Funder type
Government
Funder name
European Commission
Alternative name(s)
EC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Funder name
Millenium Pharmaceuticals Inc. (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-000615-84/results
Publication list