Clinical trial • Phase II • Oncology

MIFAMURTIDE for High-grade osteosarcoma | High-risk osteosarcoma

Phase II trial of MIFAMURTIDE for High-grade osteosarcoma | High-risk osteosarcoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
High-grade osteosarcoma | High-risk osteosarcoma
Trial Stage
Phase II
Drug Modality
Peptide/protein/enzyme | Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
13-06-2024
First CTIS Authorization Date
10-07-2024

Trial design

Randomised, open-label, post-operative chemotherapy alone (standard post-operative chemotherapy; agents mentioned in the trial documentation include cisplatin, doxorubicin hydrochloride, methotrexate, ifosfamide, etoposide). specific doses/schedules for the comparator arm are not specified in the provided data.-controlled Phase II trial across 37 sites in France.

Randomised
Yes
Open Label
Yes
Comparator
Post-operative chemotherapy alone (standard post-operative chemotherapy; agents mentioned in the trial documentation include CISPLATIN, DOXORUBICIN HYDROCHLORIDE, METHOTREXATE, IFOSFAMIDE, ETOPOSIDE). Specific doses/schedules for the comparator arm are not specified in the provided data.
Target Sample Size
315
Trial Duration For Participant
252

Eligibility

Recruits 315 paediatric patients.

Pregnancy Exclusion
Pregnancy or breast-feeding
Vulnerable Population
The trial includes minors (>2 years). Informed consent requirements: "Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure" and "Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses." Consent from parents/guardians is required for minors; assent procedures for children are not explicitly described in the available documentation.

Inclusion criteria

  • {"criterion_text":"- At diagnosis : All newly diagnosed, biopsy-proven, high-grade osteosarcoma, whatever the initial extension of the disease"}
  • {"criterion_text":"- For the randomisation : Osteosarcoma classified as high risk because of at least one risk factor"}
  • {"criterion_text":"- For the randomisation : Pre-operative chemotherapy"}
  • {"criterion_text":"- For the randomisation : Screening laboratory values must meet the following criteria (using CTCAE v5) and should be obtained within 7 days prior to randomisation"}
  • {"criterion_text":"- For the randomisation : Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 7 days prior to randomisation"}
  • {"criterion_text":"- For the randomisation : Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses."}
  • {"criterion_text":"- For the randomisation : Patient fit to undergo protocol treatment and follow-up"}
  • {"criterion_text":"- For the randomisation : Affiliation to a social insurance regimen"}
  • {"criterion_text":"- At diagnosis : Age >2 years and ≤50 years"}
  • {"criterion_text":"- At diagnosis : Normal haematological, renal, cardiac and hepatic functions"}
  • {"criterion_text":"- At diagnosis : Planned neoadjuvant chemotherapy"}
  • {"criterion_text":"- At diagnosis : Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure"}
  • {"criterion_text":"- At diagnosis : Affiliation to a social insurance regimen"}
  • {"criterion_text":"- For the randomisation : Patient with a histologically proven, confirmed by expert pathologists panel (before surgery at the latest), high-grade osteosarcoma"}
  • {"criterion_text":"- For the randomisation : Registered at diagnosis into the study"}
  • {"criterion_text":"- For the randomisation : Primary tumour resected after pre-operative chemotherapy"}

Exclusion criteria

  • {"criterion_text":"- Low grade osteosarcoma, parosteal or periosteal osteosarcoma"}
  • {"criterion_text":"- Concurrent use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs, cyclooxygenase inhibitors)"}
  • {"criterion_text":"- Inflammatory or auto-immune disease, allergy or asthma requiring a chronic use of steroid treatment that cannot be stopped"}
  • {"criterion_text":"- Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)"}
  • {"criterion_text":"- Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection"}
  • {"criterion_text":"- Prior history of other malignancies other than osteosarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years"}
  • {"criterion_text":"- Osteosarcoma with multiple metastases for whom complete removal is not expected to be feasible even after shrinkage with chemotherapy"}
  • {"criterion_text":"- Progressive disease at any site during initial pre-operative chemotherapy, confirmed before randomisation time, with exception of patients with progressive disease of the primary tumour who had a complete resection at surgery"}
  • {"criterion_text":"- Any medical condition precluding treatment with protocol post-operative chemotherapy"}
  • {"criterion_text":"- Fractional Shortening < 28% or LVEF< 50% before treatment (only for API post-operative chemotherapy) by echocardiogram or Muga scan"}
  • {"criterion_text":"- Pregnancy or breast-feeding"}
  • {"criterion_text":"- Hypersensitivity to the active substance or to any of the excipients"}
  • {"criterion_text":"- Concurrent use of immunodepressive treatment such as cyclosporine, tacrolimus or other calcineurin inhibitors"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Event-free survival (EFS) estimated from the randomisation date to the time of first event (loco-regional or distant relapse or progression, second malignancy, death from any cause). Observations will be censored at the date of last follow-up visit for the patients remaining in first complete remission.","definition_or_measurement_approach":"EFS measured from randomisation to first event (loco-regional or distant relapse or progression, second malignancy, or death from any cause); censoring at date of last follow-up for patients in first complete remission."}

Secondary endpoints

  • {"endpoint_text":"- Overall survival (OS) from the randomisation date to the date of death, whatever the cause of death.","definition_or_measurement_approach":"OS measured from randomisation to date of death from any cause."}
  • {"endpoint_text":"- Progression Free-survival (PFS) from the randomisation date to the date of disease progression (radiological or clinical) or death of any cause, whichever occurs first. Observations will be censored at the date of last follow-up visit for the patients remaining in first complete remission.","definition_or_measurement_approach":"PFS measured from randomisation to radiological or clinical progression or death; censoring at last follow-up for patients in first complete remission."}
  • {"endpoint_text":"- Feasibility of the planned treatment with calculation of cumulative dose and dose intensity of mifamurtide and chemotherapy","definition_or_measurement_approach":"Assessment of feasibility via calculation of cumulative doses and dose intensity for mifamurtide and concomitant chemotherapy as administered per protocol."}
  • {"endpoint_text":"- Safety : all adverse events (NCI-CTCAE v5) will be analysed except AE unequivocally related to the underlying disease or its progression/relapse.","definition_or_measurement_approach":"Safety assessed by analysis of all adverse events graded by NCI-CTCAE v5, excluding AEs clearly related to underlying disease or progression/relapse."}
  • {"endpoint_text":"- Long-term toxicity","definition_or_measurement_approach":"Assessment of long-term treatment-related toxicities (no detailed measurement approach specified)."}
  • {"endpoint_text":"- Biomarkers to evaluate mifamurtide mechanisms of action and resistance","definition_or_measurement_approach":"Evaluation of biomarkers through associated translational research to study mechanisms of action and resistance to mifamurtide (methods not specified in the available text)."}

Recruitment

Planned Sample Size
315
Recruitment Window Months
179
Consent Approach
Dated and signed written informed consent required prior to any study-specific procedures. For minors, consent must be provided by parents/guardians ("Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure"). A specific assent process or age-specific consent documents and languages available are not described in the provided documentation.

Geography

Total Number Of Sites
37
Total Number Of Participants
315

France

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
10-07-2024
Processing Time Days
14
Number Of Sites
37
Number Of Participants
315

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
Oncologie pédiatrique
Principal Investigator Name
Gabriel REVON-RIVIERE
Principal Investigator Email
gabriel.revon-riviere@ap-hm.fr
Contact Person Name
Gabriel REVON-RIVIERE
Contact Person Email
gabriel.revon-riviere@ap-hm.fr
Site Name
Institut Gustave Roussy
Department Name
Cancérologie de l’enfant et l’adolescent
Principal Investigator Name
Nathalie GASPAR
Principal Investigator Email
Nathalie.GASPAR@gustaveroussy.fr
Contact Person Name
Nathalie GASPAR
Site Name
Institut De Cancerologie De Lorraine
Department Name
Oncologie Médicale
Principal Investigator Name
Anne KIEFFER
Principal Investigator Email
a.kieffer@nancy.unicancer.fr
Contact Person Name
Anne KIEFFER
Contact Person Email
a.kieffer@nancy.unicancer.fr
Site Name
Centre Oscar Lambret
Department Name
Onco-pédiatrie
Principal Investigator Name
Cyril LERVAT
Principal Investigator Email
c-lervat@o-lambret.fr
Contact Person Name
Cyril LERVAT
Contact Person Email
c-lervat@o-lambret.fr
Site Name
Institut Regional Du Cancer De Montpellier
Department Name
Oncologie Médicale
Principal Investigator Name
Nelly FIRMIN
Principal Investigator Email
Nelly.firmin@icm.unicancer.fr
Contact Person Name
Nelly FIRMIN
Contact Person Email
Nelly.firmin@icm.unicancer.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie Médicale
Principal Investigator Name
Emmanuelle BOMPAS
Principal Investigator Email
emmanuelle.bompas@ico.unicancer.fr
Contact Person Name
Emmanuelle BOMPAS
Site Name
Institut De Cancerologie Strasbourg Europe
Department Name
Onco-hématologie
Principal Investigator Name
Jean-Emmanuel KURTZ
Principal Investigator Email
je.kurtz@icans.eu
Contact Person Name
Jean-Emmanuel KURTZ
Contact Person Email
je.kurtz@icans.eu
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Joy BENADIBA
Principal Investigator Email
benadiba.j@chu-nice.fr
Contact Person Name
Joy BENADIBA
Contact Person Email
benadiba.j@chu-nice.fr
Site Name
Centre Leon Berard
Department Name
Hémato-oncologie pédiatrique
Principal Investigator Name
Perrine MAREC-BERARD
Principal Investigator Email
perrine.marec-berard@ihope.fr
Contact Person Name
Perrine MAREC-BERARD
Contact Person Email
perrine.marec-berard@ihope.fr
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Claire PLUCHARD
Principal Investigator Email
cpluchart@chu-reims.fr
Contact Person Name
Claire PLUCHARD
Contact Person Email
cpluchart@chu-reims.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Natacha ENTZ-WERLE
Principal Investigator Email
natacha.entz-werle@chru-strasbourg.fr
Contact Person Name
Natacha ENTZ-WERLE
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Oncologie Médicale
Principal Investigator Name
Florence DUFFAUD
Principal Investigator Email
florence.duffaud@ap-hm.fr
Contact Person Name
Florence DUFFAUD
Contact Person Email
florence.duffaud@ap-hm.fr
Site Name
Centr Georges Francois Leclerc
Department Name
Oncologie Médicale
Principal Investigator Name
Alice HERVIEU
Principal Investigator Email
ahervieu@cgfl.fr
Contact Person Name
Alice HERVIEU
Contact Person Email
ahervieu@cgfl.fr
Site Name
Oncopole Claudius Regaud
Department Name
Oncologie Médicale
Principal Investigator Name
Thibaud VALENTIN
Principal Investigator Email
Valentin.thibaud@iuct-oncopole.fr
Contact Person Name
Thibaud VALENTIN
Site Name
CHU Besancon
Department Name
Hémato-Onco-pédiatrie
Principal Investigator Name
Sébastien KLEIN
Principal Investigator Email
s1klein@chu-besancon.fr
Contact Person Name
Sébastien KLEIN
Contact Person Email
s1klein@chu-besancon.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Laure SAUMET
Principal Investigator Email
l-saumet@chu-montpellier.fr
Contact Person Name
Laure SAUMET
Contact Person Email
l-saumet@chu-montpellier.fr
Site Name
Centre Leon Berard
Department Name
Oncologie Médicale
Principal Investigator Name
Jean-Yves BLAY
Principal Investigator Email
jean-yves.blay@lyon.unicancer.fr
Contact Person Name
Jean-Yves BLAY
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Leslie ANDRY
Principal Investigator Email
andry.leslie@chu-amiens.fr
Contact Person Name
Leslie ANDRY
Contact Person Email
andry.leslie@chu-amiens.fr
Site Name
Pellegrin Hospital
Department Name
Hémato-oncologie pédiatrique
Principal Investigator Name
Cecile VERITE
Principal Investigator Email
cecile.verite@chu-bordeaux.fr
Contact Person Name
Cecile VERITE
Contact Person Email
cecile.verite@chu-bordeaux.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Hématologie et Cancérologie pédiatrique
Principal Investigator Name
Christophe PIGUET
Principal Investigator Email
christophe.piguet@chu-limoges.fr
Contact Person Name
Christophe PIGUET
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Marianna DEPARIS
Principal Investigator Email
deparis-m@chu-caen.fr
Contact Person Name
Marianna DEPARIS
Contact Person Email
deparis-m@chu-caen.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Hémato-Immuno-Oncologie Pédiatrique
Principal Investigator Name
Pascale SCHNEIDER
Principal Investigator Email
pascale.schneider@chu-rouen.fr
Contact Person Name
Pascale SCHNEIDER
Contact Person Email
pascale.schneider@chu-rouen.fr
Site Name
Centre De Lutte Contre Le Cancer Eugene Marquis
Department Name
Oncologie Médicale
Principal Investigator Name
Christophe PERRIN
Principal Investigator Email
c.perrin@rennes.unicancer.fr
Contact Person Name
Christophe PERRIN
Contact Person Email
c.perrin@rennes.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Morgane CLEIREC
Principal Investigator Email
morgane.cleirec@chu-nantes.fr
Contact Person Name
Morgane CLEIREC
Contact Person Email
morgane.cleirec@chu-nantes.fr
Site Name
CHRU De Nancy
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Ludovic MANSUY
Principal Investigator Email
lu.mansuy@chru-nancy.fr
Contact Person Name
Ludovic MANSUY
Contact Person Email
lu.mansuy@chru-nancy.fr
Site Name
Institut Godinot
Department Name
Oncologie Médicale
Principal Investigator Name
Pauline SOIBINET-OUDOT
Principal Investigator Email
Pauline.soibinet@reims.unicancer.fr
Contact Person Name
Pauline SOIBINET-OUDOT
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Hema-Immuno-Oncologie
Principal Investigator Name
Marie-Pierre CASTEX
Principal Investigator Email
castex.mp@chu-toulouse.fr
Contact Person Name
Marie-Pierre CASTEX
Contact Person Email
castex.mp@chu-toulouse.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Florence NEUMANN
Principal Investigator Email
florent.neumann@chu-dijon.fr
Contact Person Name
Florence NEUMANN
Contact Person Email
florent.neumann@chu-dijon.fr
Site Name
Centre Hospitalier Regional D'Angers
Department Name
Oncologie pédiatrique
Principal Investigator Name
Stephanie PROUST
Principal Investigator Email
stproust@chu-angers.fr
Contact Person Name
Stephanie PROUST
Contact Person Email
stproust@chu-angers.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Chrystelle DUPRAZ
Principal Investigator Email
c.dupraz@chu-poitiers.fr
Contact Person Name
Chrystelle DUPRAZ
Contact Person Email
c.dupraz@chu-poitiers.fr
Site Name
Institut Bergonie
Department Name
Oncologie Médicale
Principal Investigator Name
Antoine ITALIANO
Principal Investigator Email
a.italiano@bordeaux.unicancer.fr
Contact Person Name
Antoine ITALIANO
Site Name
Trousseau Hospital
Department Name
Hématologie et Oncologie
Principal Investigator Name
Marie-Dominique TABONE
Principal Investigator Email
marie-dominique.tabone@aphp.fr
Contact Person Name
Marie-Dominique TABONE
Contact Person Email
marie-dominique.tabone@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Service de médecine de l’enfant et de l’adolescent, Unité d’hémato-oncologie
Principal Investigator Name
Sophie TAQUE
Principal Investigator Email
sophie.taque@chu-rennes.fr
Contact Person Name
Sophie TAQUE
Contact Person Email
sophie.taque@chu-rennes.fr
Site Name
Grenoble University Hospital Center
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Severine BOBILLIER-CHAUMONT
Principal Investigator Email
sbobillierchaumont@chu-grenoble.fr
Contact Person Name
Severine BOBILLIER-CHAUMONT
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Cancérologie
Principal Investigator Name
Pascaline BOUDOU ROUQUETTE
Principal Investigator Email
pascaline.boudou@aphp.fr
Contact Person Name
Pascaline BOUDOU ROUQUETTE
Contact Person Email
pascaline.boudou@aphp.fr
Site Name
Institut Gustave Roussy
Department Name
Oncologie Médicale
Principal Investigator Name
Sarah DUMONT
Principal Investigator Email
sarah.dumont@gustaveroussy.fr
Contact Person Name
Sarah DUMONT
Contact Person Email
sarah.dumont@gustaveroussy.fr
Site Name
Institut Curie
Department Name
Oncologie pédiatrique
Principal Investigator Name
Sarah WINTER
Principal Investigator Email
Sarah.Winter@curie.fr
Contact Person Name
Sarah WINTER
Contact Person Email
Sarah.Winter@curie.fr
Site Name
Centre Hospitalier Universitaire De La Reunion
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Stéphanie GOURDON
Principal Investigator Email
stephanie.gourdon@chu-reunion.fr
Contact Person Name
Stéphanie GOURDON
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Oncologie Médicale
Principal Investigator Name
Bérengère NARCISO
Principal Investigator Email
berengere.narciso@univ-tours.fr
Contact Person Name
Bérengère NARCISO
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hematologie et Oncologie pédiatrique
Principal Investigator Name
Jill SERRE
Principal Investigator Email
j.serre@chu-tours.fr
Contact Person Name
Jill SERRE
Contact Person Email
j.serre@chu-tours.fr
Site Name
Institut Paoli Calmettes
Department Name
Oncologie Médicale
Principal Investigator Name
François BERTUCCI
Principal Investigator Email
bertuccif@ipc.unicancer.fr
Contact Person Name
François BERTUCCI
Contact Person Email
bertuccif@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Hématologie et Cancérologie pédiatrique
Principal Investigator Name
Claire BERGER
Principal Investigator Email
claire.berger@chu-st-etienne.fr
Contact Person Name
Claire BERGER
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Onco-hématologie pédiatrique
Principal Investigator Name
Justyna KANOLD
Principal Investigator Email
jkanold@chu-clermontferrand.fr
Contact Person Name
Justyna KANOLD
Contact Person Email
jkanold@chu-clermontferrand.fr
Site Name
Institut Curie
Department Name
Oncologie Médicale
Principal Investigator Name
Sophie PIPERNO-NEUMANN
Principal Investigator Email
sophie.piperno-neumann@curie.fr
Contact Person Name
Sophie PIPERNO-NEUMANN

Sponsor

Primary sponsor

Full Name
Unicancer
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Third parties

  • {"country":"","full_name":"PHRC","duties_or_roles":"","organisation_type":""}
  • {"country":"","full_name":"TAKEDA","duties_or_roles":"","organisation_type":""}

Investigational products

Investigational Product Name
MEPACT 4 mg powder for concentrate for dispersion for infusion
Active Substance
MIFAMURTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
EU/1/08/502/001
Maximum Dose
2 mg/m2 milligram(s)/sq. meter (maxDailyDoseAmount value provided)
Investigational Product Name
DOXORUBICIN HYDROCHLORIDE
Active Substance
DOXORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
60 mg/m2 milligram(s)/sq. meter (maxDailyDoseAmount value provided)
Investigational Product Name
IFOSFAMIDE
Active Substance
IFOSFAMIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
3 gm/m2 gram(s)/square meter (maxDailyDoseAmount value provided)
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
100 mg/m2 milligram(s)/sq. meter (maxDailyDoseAmount value provided)
Investigational Product Name
METHOTREXATE
Active Substance
METHOTREXATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
12 gm/m2 gram(s)/square meter (maxDailyDoseAmount value provided)
Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
75 mg/m2 milligram(s)/sq. meter (maxDailyDoseAmount value provided)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.