European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART)
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|ClinicalTrials.gov Identifier: NCT02813135|
Recruitment Status : Recruiting
First Posted : June 24, 2016
Last Update Posted : August 13, 2018
The first molecular profiling protocols have been launched in Europe (MOSCATO-01 (Geoerger 2014), MAPPYACTS, INFORM, iTHER, SM-PAEDS, etc.) determining multiple actionable alterations in pediatric recurrent cancers. Increasingly, stratified approaches are being implemented to enrich clinical trials of molecularly targeted agents and possibly improve outcomes in specific populations i.e. a molecularly enriched/predictive biomarker-driven approach. The diversity and heterogeneity of the detected molecular alterations and the low number of pediatric patients mandate an adapted, innovative trial design for the attributed treatment options in order to satisfy the current unmet medical need.
This basket trial is designed to cover the targeting of several survival pathways in oncogenesis that are currently not adequately employed for pediatric patients in Europe.
|Condition or disease||Intervention/treatment||Phase|
|Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies||Drug: Ribociclib Drug: Topotecan Drug: Temozolomide Drug: Everolimus Drug: AZD1775 Drug: Carboplatin Drug: Olaparib Drug: Irinotecan Drug: Nivolumab Drug: Enasidenib Drug: Lirilumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||397 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors|
|Actual Study Start Date :||August 3, 2016|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||January 2022|
Experimental: ARM A. Ribociclib + Topotecan and Temozolomide
Topotecan iv QD and temozolomide capsules orally QD Days 1 to 5; Ribociclib capsules or oral solution orally QD from Day 6 to 20 of a 28 day cycle.
Experimental: ARM B. Ribociclib + Everolimus
Ribociclib capsules or oral solution orally QD for 21 days of each 28 day cycle; Everolimus orodispersible tablets orally QD for 28 days.
Experimental: ARM C. AZD1775 + Carboplatin
AZD1775 capsules orally BID 3 days on / 4 days off in week 1; Carboplatin iv QD AUC 5 on Day 1 of a 21 day cycle.
Experimental: ARM D. Olaparib + Irinotecan
Olaparib tablets orally BID on Day 1-10 of a 21 day cycle; Irinotecan iv QD Day 4-8 of a 21 day cycle.
Experimental: Arm I. Enasidenib
Enasidenib orally on a continuous dosing once daily (QD) per 28 day cycle.
Experimental: Arm J. Lirilumab + Nivolumab
Nivolumab iv QD every 2 weeks of a 28 day cycle (Days 1 and 15); Lirilumab iv QD every 4 weeks of a 28 day cycle (Day 1)
- Objective tumor response [ Time Frame: Objective tumor response will be measured according to RECIST 1.1 , RANO for HGG and INRC for NB after 56 day ]
- Time to progression [ Time Frame: Time to progression will be measured according to RECIST 1.1 , RANO for HGG and INRC for NB after after 56 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02813135
|Contact: Birgit Geoerger, MD||1 42 11 4661 ext +firstname.lastname@example.org|
|Contact: Xavier Paoletti, MD||1 42 11 6564 ext +email@example.com|
|Villejuif, Val De Marne, France, 94805|
|Contact: Birgit Geoerger, MD 1 42 11 4661 ext +33 firstname.lastname@example.org|
|Contact: Xavier Paoletti, MD 1 42 11 6564 ext +33 email@example.com|
|Principal Investigator: Birgit Geoerger, MD|
|University Children's Hospitalermany||Not yet recruiting|
|Contact: Olaf Witt, MD 6221 56 4555 ext +49 O.Witt@Dkfz-Heidelberg.de|
|Fondazione IRCCS Istituto Nazionale dei Tumori||Not yet recruiting|
|Contact: Michela Casanova, MD 02 23 90 25 94 ext +39 Michela.Casanova@istitutotumori.mi.it|
|Erasmus MC, Sophia Children's Hospital||Not yet recruiting|
|Contact: Michel Zwaan, MD 10 703 6691 ext +31 firstname.lastname@example.org|
|Unidad de Oncología Pediátrica Hospital Niño Jesús||Not yet recruiting|
|Madrid, Spain, 28009|
|Contact: Francisco Bautista, MD 915 035 900 ext +43 email@example.com|
|Pediatric and Adolescent Oncology The Royal Marsden Hospital||Not yet recruiting|
|Sutton, United Kingdom|
|Contact: Lynley Marshall, MD 208 661 3678 ext +44 Lynley.Marshall@icr.ac.uk|
|Study Chair:||Birgit Geoerger, MD||Gustave ROUSSY|