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Failed to recruit sufficient numbers of patients in the funded period
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| Name | Class |
|---|---|
| Millennium: The Takeda Oncology Company | INDUSTRY |
| National Institute for Health Research, United Kingdom | OTHER_GOV |
| Oxford University Hospitals NHS Trust | OTHER |
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This is a Bayesian designed multi-arm, multi-centre, open label phase II study. The target sample size of 40 patients will be recruited from up to 8 EU countries, but this may be revised in light of the interim analysis. Patients with relapsed or metastatic osteosarcoma will be divided into three treatment groups. They will all either have surgery or a biopsy before and after six weeks exposure to either Mifamurtide alone, Ifosfamide alone, or Mifamurtide combined with Ifosfamide. They will then receive further treatment to a maximum of 42 or 36 weeks in total (depending on Arm), with all patients being able to receive 36 weeks of Mifamurtide treatment.
Osteosarcoma (OS) is the most common primary tumour arising from bones. There is currently no approved treatment other than surgery for metastatic or recurrent osteosarcoma refractory to chemotherapy. Patients deemed unresectable normally receive chemotherapy prior to attempted resection. The addition of chemotherapy to surgery for metastatic or recurrent osteosarcoma may improve response rates. MEPACT (Mifamurtide, MTP-PE) is licensed for use in the adjuvant osteosarcoma setting; indicated in children, adolescents and young adults for the treatment of high-grade resectable non-metastatic osteosarcoma after macroscopically complete surgical resection. It is used in combination with post-operative multi-agent chemotherapy. 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. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A. Mifamurtide only | Experimental | 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. |
|
| B. Ifosfamide (Followed by Mifamurtide) | Experimental | 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. |
|
| C. Ifosfamide + Mifamurtide | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mifamurtide | Drug |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| Biological Response Data Based on Pharmacodynamic Endpoints on Tumour Biopsy Material | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Radiological Response Based on RECIST v1.1 | 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 |
Not provided
Inclusion Criteria:
Lab Test Value required
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.
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| Name | Affiliation | Role |
|---|---|---|
| Bass Hassan, BMBCh FRCP | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pediatric Hematology and Oncology, University Hospital Münster | Münster | 48149 | Germany | |||
| Istituti Ortopedici Rizzoli |
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | A. Mifamurtide Only | Patients receive 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. Mifamurtide |
| FG001 | B. Ifosfamide (Followed by Mifamurtide) | Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. 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 must be started 24 hours prior to mifamurtide. Mifamurtide should be 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. Mifamurtide Ifosfamide |
| FG002 | C. Ifosfamide + Mifamurtide | Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be 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 infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | A. Mifamurtide Only | Patients receive 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. Mifamurtide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Biological Response Data Based on Pharmacodynamic Endpoints on Tumour Biopsy Material | Biological response data based on pharmacodynamic endpoints on tumour biopsy material including macrophage infiltration and innate immune activation. | Insufficient number of participants for events for both primary and secondary objectives. The study stopped prematurely because of poor recruitment, meaning that no complete statistical analysis was possible as there were insufficient events and data were not collected. | Posted | Change from Baseline to after 6 weeks of treatment |
|
Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment.
An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | A. Mifamurtide Only | Patients receive 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. Mifamurtide |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
Early termination leading to small numbers of subjects analyzed. This was due to a poor recruitment speed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joint Research Office | University of Oxford | +441865572245 | ctrg@admin.ox.ac.uk |
Not provided
| ID | Term |
|---|---|
| D012516 | Osteosarcoma |
| ID | Term |
|---|---|
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C037144 | mifamurtide |
| D007069 | Ifosfamide |
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
Not provided
Not provided
| European Commission |
| OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Ifosfamide |
| Drug |
|
| 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) | 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) | 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 | 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 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). | 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. |
| Bologna |
| Emilia-Romagna |
| 40136 |
| Italy |
| Department of Clinical Oncology, Leiden University Medical Center | Leiden | Postzone K1-P | P.O. Box 9600 | Netherlands |
| Radium Hospital, Oslo University | Oslo | 0310 | Norway |
| Leeds Teaching Hospitals NHS Trust | Leeds | LS9 7TF | United Kingdom |
| University College London Hospitals NHS Foundation Trust | London | NW1 2BU | United Kingdom |
| Christie Hospital NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| Oxford University Hospitals NHS Foundations Trust | Oxford | OX3 7LE | United Kingdom |
| Withdrawal by Subject |
|
| BG001 | B. Ifosfamide (Followed by Mifamurtide) | Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. 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 must be started 24 hours prior to mifamurtide. Mifamurtide should be 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. Mifamurtide Ifosfamide |
| BG002 | C. Ifosfamide + Mifamurtide | Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be 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 infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| WHO Performance Status | WHO performance status classification The WHO performance status classification categorises patients as: 0. able to carry out all normal activity without restriction
| Count of Participants | Participants |
|
| Histology/Cytological type | International classification of diseases for oncology. ICD-O-3 online | Count of Participants | Participants |
|
| Primary Site | Count of Participants | Participants |
|
| Disease stage at screening - Metastatic | Count of Participants | Participants |
|
| Tumour size at baseline (sum of longest diameters) (mm) | Median | Inter-Quartile Range | mm |
|
| Prior chemotherapy | Count of Participants | Participants |
|
| Prior radiotherapy | Count of Participants | Participants |
|
| Prior surgery | Count of Participants | Participants |
|
| OG001 | B. Ifosfamide (Followed by Mifamurtide) | Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. 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 must be started 24 hours prior to mifamurtide. Mifamurtide should be 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. Mifamurtide Ifosfamide |
| OG002 | C. Ifosfamide + Mifamurtide | Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be 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 infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide |
|
| Primary | Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria | 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 | All patients are included since this is an intention to treat analysis. | Posted | Count of Participants | Participants | Change from Baseline to after 6 weeks of treatment |
|
|
|
| Secondary | Objective Radiological Response Based on RECIST v1.1 | 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 | The end of treatment visit was completed by patients who were deemed to progress or withdrew from trial treatment at a time that a scheduled scan was not due to be taken. This end of treatment visit was used to confirm radiological progression. | Posted | Count of Participants | Participants | Change from Baseline to after 12, 18, 24 & 36 weeks and end of treatment visit |
|
|
|
| Secondary | Number of Patients Experiencing a Grade 3 or More Severe Adverse Event (Graded According to CTCAE Criteria v4.0) | 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. | Intention to treat | Posted | Count of Participants | Participants | Up to 42 weeks |
|
|
|
| Secondary | Number of Patients Experiencing a Laboratory Abnormality (Grade 3-4) | 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). | Intention to treat | Posted | Count of Participants | Participants | Up to 42 weeks |
|
|
|
| Secondary | Disease Specific Overall Survival | Median time from death attributed to the disease. Censored at last known time alive or death from other causes. | Intention to treat | Posted | Median | 95% Confidence Interval | months | Up to 42 weeks |
|
|
|
| Secondary | Progression Free Survival | 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. | Intention to treat | Posted | Median | 95% Confidence Interval | months | Up to 42 weeks |
|
|
|
| Secondary | Biological Response (Systemic Levels of Mifamurtide Activated Cytokines). | Biological response based on systemic levels of mifamurtide activated cytokines. | Insufficient number of participants for events for both primary and secondary objectives. The study stopped prematurely because of poor recruitment, meaning that no complete statistical analysis was possible as there were insufficient events and data were not collected. | Posted | During screening, and weeks 1, 4, 6 and 7. Then every 3 weeks during treatment. |
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | B. Ifosfamide (Followed by Mifamurtide) | Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. 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 must be started 24 hours prior to mifamurtide. Mifamurtide should be 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. Mifamurtide Ifosfamide | 0 | 2 | 2 | 2 | 2 | 2 |
| EG002 | C. Ifosfamide + Mifamurtide | Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be 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 infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide | 2 | 3 | 2 | 3 | 3 | 3 |
| Pseudomonas infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypophosphataemia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fever | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Flu like symptoms | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Shivering | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Central line infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Infected toe | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Muscle weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Taste altered | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D009369 | Neoplasms |
| D012509 | Sarcoma |
| D006846 |
| Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Patient did not reach endpoint |
|
| Patient progressed prior to time point |
|
| Progressive Disease (PD) |
|
| Patient did not reach endpoint |
|
| Week 18 |
|
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| Week 24 |
|
|
| Week 36 |
|
|
| End of Treatment visit (prior to week 6) |
|
|