Clinical Trial: A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Mechanistic Study Of Mifamurtide (MTP-PE) In Patients With Metastatic And/Or Recurrent Osteosarcoma

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: University of Oxford

Current Primary Outcome:

  • 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.
  • Radiological response defined as complete or partial response and assessed using RECIST criteria [ Time Frame: Change from Baseline to after 6 weeks of treatment ]
    Radiological response defined as complete or partial response and assessed using RECIST criteria
  • Objective radiological response based on RECIST 1.1 [ Time Frame: Change from Baseline to after 6, 12, 18, 24 & 36 weeks of treatment ]
    Objective radiological response based on RECIST 1.1


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Toxicity (graded according to the CTCAE criteria) [ Time Frame: Up to 42 weeks ]
    Toxicity measured and graded according to the CTCAE criteria
  • Laboratory abnormalities (grade 3-4) [ Time Frame: Up to 42 weeks ]
    Laboratory abnormalities grade 3 and 4
  • Disease specific overall survival [ Time Frame: Up to 42 weeks ]
    The time from registration/randomisation to death due to the disease. Surviving patients and deaths due to other cause 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.
  • Progression free survival on serial CT scan [ 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 progression as (defined by RECIST criterion) 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.


Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: March 16, 2015
Date Started: October 2014
Date Completion:
Last Updated: March 21, 2017
Last Verified: March 2017