- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02441309
A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS) (MEMOS)
A Mechanistic Study Of Mifamurtide (MTP-PE) In Patients With Metastatic And/Or Recurrent Osteosarcoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Münster, Germany, 48149
- Pediatric Hematology and Oncology, University Hospital Münster
-
-
-
-
Emilia-Romagna
-
Bologna, Emilia-Romagna, Italy, 40136
- Istituti Ortopedici Rizzoli
-
-
-
-
Postzone K1-P
-
Leiden, Postzone K1-P, Netherlands, P.O. Box 9600
- Department of Clinical Oncology, Leiden University Medical Center
-
-
-
-
-
Oslo, Norway, 0310
- Radium Hospital, Oslo University
-
-
-
-
-
Leeds, United Kingdom, LS9 7TF
- Leeds Teaching Hospitals NHS Trust
-
London, United Kingdom, NW1 2BU
- University College London Hospitals NHS Foundation Trust
-
Manchester, United Kingdom, M20 4BX
- Christie Hospital NHS Foundation Trust
-
Oxford, United Kingdom, OX3 7LE
- Oxford University Hospitals NHS Foundations Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
- Life expectancy of at least 3 months.
- WHO performance score of 0 - 2.
- The patient is willing and able to comply with the protocol and scheduled follow-up visits and examinations.
- Written (signed and dated) informed consent.
- Cardiac shortening fraction ≥ 28% or ejection fraction ≥ 45%
- Renal function is adequate for ifosfamide treatment (GFR as per table below, other renal function screening tests as per local practice)
- Haematological and biochemical indices within the ranges shown below:
Lab Test Value required
- Haemoglobin (Hb) ≥ 9 g/dL (Previous transfusion is allowed)
- Absolute neutrophil count (ANC) >=1.0 x 10*9/L without growth factor support
- Platelet count > 80.x 10*9/L (Previous transfusion is allowed)
- Total bilirubin <1.5 times the upper limit of normal (ULN) for age (except for Gilbert's syndrome patients)
- Serum alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) <2.5 × ULN for age, <2.5 × ULN for age
- Serum creatinine Normal range for age
- Glomerular filtration rate (GFR) (calculated as 51Cr-EDTA/99mTc-DTPA clearance) >40ml/min if deemed resectable (for Arm A), >60ml/min if not deemed resectable (for Arm B or C)
Exclusion Criteria:
- 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 (see section 5.1 Informed consent - Contraceptive/ Pregnancy counselling).
- 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 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
- Treatment with any other investigational agent, or participation in another interventional clinical trial within 21 days prior to enrolment.
- 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.
- 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.
- Any other active malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions.
Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- mifamurtide-like drugs include GCSF, GMCSF, interferon and other macrophage activating molecules.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A. Mifamurtide only
Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. |
|
Experimental: B. Ifosfamide (Followed by Mifamurtide)
Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. |
|
Experimental: C. Ifosfamide + Mifamurtide
Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, each given at least 3 days apart, for 6 weeks. Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, given at least 3 days apart, for 6 weeks. Ifosfamide infusion started 24 hours prior to mifamurtide. Mifamurtide given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biological Response Data Based on Pharmacodynamic Endpoints on Tumour Biopsy Material
Time Frame: Change from Baseline to after 6 weeks of treatment
|
Biological response data based on pharmacodynamic endpoints on tumour biopsy material including macrophage infiltration and innate immune activation.
|
Change from Baseline to after 6 weeks of treatment
|
Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria
Time Frame: Change from Baseline to after 6 weeks of treatment
|
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT or MRI: Complete Response (CR): Disappearance of all target and non-target lesions Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions, AND no evidence of progression in non-target lesions, AND no new lesions Stable Disease (SD): sum of longest diameter of target lesions between PR and PD values, AND no evidence of progression in non-target lesions, AND no new lesions Progressive Disease (PD): >20% increase in the sum of the longest diameter of target lesions, OR evidence of progression in non-target lesions, OR evidence of new lesions |
Change from Baseline to after 6 weeks of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Radiological Response Based on RECIST v1.1
Time Frame: Change from Baseline to after 12, 18, 24 & 36 weeks and end of treatment visit
|
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT or MRI: Complete Response (CR): Disappearance of all target and non-target lesions Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions, AND no evidence of progression in non-target lesions, AND no new lesions Stable Disease (SD): sum of longest diameter of target lesions between PR and PD values, AND no evidence of progression in non-target lesions, AND no new lesions Progressive Disease (PD): >20% increase in the sum of the longest diameter of target lesions, OR evidence of progression in non-target lesions, OR evidence of new lesions |
Change from Baseline to after 12, 18, 24 & 36 weeks and end of treatment visit
|
Number of Patients Experiencing a Grade 3 or More Severe Adverse Event (Graded According to CTCAE Criteria v4.0)
Time Frame: Up to 42 weeks
|
Toxicity measured and graded according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Grade refers to the severity of the adverse event. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe; medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling or limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. |
Up to 42 weeks
|
Number of Patients Experiencing a Laboratory Abnormality (Grade 3-4)
Time Frame: Up to 42 weeks
|
A laboratory abnormality is defined as an adverse event of grade 3 or 4 identified by a laboratory test of participant blood samples. Adverse events were graded according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE). |
Up to 42 weeks
|
Disease Specific Overall Survival
Time Frame: Up to 42 weeks
|
Median time from death attributed to the disease.
Censored at last known time alive or death from other causes.
|
Up to 42 weeks
|
Progression Free Survival
Time Frame: Up to 42 weeks
|
Time from randomisation for deemed non-resectable groups, or time from registration for deemed resectable group to first event, where an event is Progressive Disease as (defined by RECIST criterion v1.1) or death due to any cause. Patients who have not had an event will be censored at their last follow-up date. Patients lost to follow-up without an event will be censored at the date of their last consultation. Progressive disease according to RECIST v1.1 is defined as a >=20% increase in the sum of long diameters of target lesions, OR progression of non-target lesions, OR evidence of new lesions. |
Up to 42 weeks
|
Biological Response (Systemic Levels of Mifamurtide Activated Cytokines).
Time Frame: During screening, and weeks 1, 4, 6 and 7. Then every 3 weeks during treatment.
|
Biological response based on systemic levels of mifamurtide activated cytokines.
|
During screening, and weeks 1, 4, 6 and 7. Then every 3 weeks during treatment.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bass Hassan, BMBCh FRCP, University of Oxford
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Sarcoma
- Osteosarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Adjuvants, Immunologic
- Ifosfamide
- Mifamurtide
Other Study ID Numbers
- OCTO_039
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Osteosarcoma
-
Klinikum StuttgartKlinikum Kassel GmbH (COSS-Biobank)Not yet recruitingOsteosarcoma | High Grade Sarcoma | Recurrent Osteosarcoma | Bone Sarcoma | Undifferentiated Pleomorphic Sarcoma | Bone Tumor | Extraskeletal Osteosarcoma | Osseous Sarcoma | Parosteal Osteosarcoma | Osteoblastic Osteosarcoma | Chondroblastic Osteosarcoma | Fibroblastic Osteosarcoma | Conventional Osteosarcoma | Conventional... and other conditions
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Refractory Osteosarcoma | Stage IV Osteosarcoma AJCC v7 | Stage IVA Osteosarcoma AJCC v7 | Stage IVB Osteosarcoma AJCC v7 | Metastatic OsteosarcomaUnited States, Canada, Puerto Rico
-
M.D. Anderson Cancer CenterRecruitingRecurrent Osteosarcoma | Refractory Osteosarcoma | Metastatic Osteosarcoma | Unresectable Osteosarcoma | Locally Advanced OsteosarcomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Not yet recruitingMetastatic Osteosarcoma | Localized Osteosarcoma | Unresectable Osteosarcoma | Resectable Osteosarcoma
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized Osteosarcoma | Osteoblastic OsteosarcomaUnited States
-
National Cancer Institute (NCI)SuspendedMetastatic Osteosarcoma | Localized Osteosarcoma | High Grade Osteosarcoma | Secondary OsteosarcomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Ewing Sarcoma | Recurrent Osteosarcoma | Stage III Osteosarcoma AJCC v7 | Stage IV Osteosarcoma AJCC v7 | Stage IVA Osteosarcoma AJCC v7 | Stage IVB Osteosarcoma AJCC v7 | Metastatic Osteosarcoma | Metastatic Ewing Sarcoma | Unresectable Ewing Sarcoma | Unresectable OsteosarcomaFrance
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States
-
Sarcoma Alliance for Research through CollaborationActive, not recruitingOsteosarcoma | Osteosarcoma Recurrent | Osteosarcoma Metastatic | Osteosarcoma in ChildrenUnited States
Clinical Trials on Mifamurtide
-
Millennium Pharmaceuticals, Inc.Completed
-
Memorial Sloan Kettering Cancer CenterAvailable
-
Millennium Pharmaceuticals, Inc.Terminated
-
Italian Sarcoma GroupActive, not recruiting
-
UNICANCERActive, not recruiting