Condition category
Cancer
Date applied
18/09/2014
Date assigned
18/09/2014
Last edited
19/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

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

14/SC/0255; First MREC approval date 13/06/2014

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

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 measures

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

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

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Wellcome Trust Centre for Human Genetics
Oxford
OX3 7BN
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

European Commission

Alternative name(s)

EC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes