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Study of Re-irradiation at Relapse Versus RT and Multiple Elective rt Courses (DIPG)

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ClinicalTrials.gov Identifier: NCT03620032
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : August 8, 2018
Sponsor:
Collaborators:
University of Roma La Sapienza
Johannes Gutenberg University Mainz
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Wuerzburg University Hospital
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary:
Prospective, non-blinded, randomised two cohorts study on the efficacy of two different radiotherapy schedule for DIPG by using the same concomitant and post-radiotherapy systemic treatment.

Condition or disease Intervention/treatment Phase
Diffuse Intrinsic Pontine Glioma Drug: Nimotuzumab Drug: Vinorelbine Other: Radiotherapy Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, non-blinded, randomised two cohorts study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Randomized Study of RT and Reirradiation at Relapse vs Multiple Elective RT Courses With Same Concomitant CT for Newly Diagnosed
Actual Study Start Date : November 2, 2015
Estimated Primary Completion Date : November 2, 2024
Estimated Study Completion Date : November 2, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Vinorelbine

Arm Intervention/treatment
Standard treatment
Nimotuzumab 150 mg /mq/d as iv weekly and Vinorelbine 20 mg/mq/d weekly, in week 1-12 (Induction phase).If not progression Nimotuzumab 150 mg/m2 as iv and Vinorelbine 25 mg/m²/d as iv until progression or maximum at week 108; in case of non-progressive disease re-irradiation 1 for a total of 19.8 Gy from week 26 to week 28; in case of non-progressive disease: re-irradiation 2 for a total of 19.8 Gy from week 46 to week 48. Irradiation will be scheduled to begin in the 3rd week after starting the nimotuzumab and vinorelbine treatment. For the first course, a total dose of 36 Gy will be delivered, in 1.8 Gy daily fractions 5 days a week.
Drug: Nimotuzumab
humanized therapeutic monoclonal antibody against epidermal growth factor receptor (EGFR)
Other Name: humanized therapeutic monoclonal antibody

Drug: Vinorelbine
Chemotherapy
Other Name: Chemotherapy

Other: Radiotherapy
RADIOTHERAPY SCHEDULE IS DESCRIBED FOR BOTH GROUPS IN THE PERAGRAPH TITLET ARMS

Experimental: Experimental treatment
Nimotuzumab 150 mg /mq/d as iv weekly and Vinorelbine 20 mg/mq/d weekly, in week 1-12 (Induction phase).If not progression Nimotuzumab 150 mg/m2 as iv and Vinorelbine 25 mg/m²/d as iv until progression or maximum at week 108; in case of non-progressive disease re-irradiation 1 for a total of 19.8 Gy from week 26 to week 28; in case of non-progressive disease: re-irradiation 2 for a total of 19.8 Gy from week 46 to week 48. Irradiation will be scheduled to begin in the 3rd week after starting the nimotuzumab and vinorelbine treatment. For the first course, a total dose of 36 Gy will be delivered, in 1.8 Gy daily fractions 5 days a week.
Drug: Nimotuzumab
humanized therapeutic monoclonal antibody against epidermal growth factor receptor (EGFR)
Other Name: humanized therapeutic monoclonal antibody

Drug: Vinorelbine
Chemotherapy
Other Name: Chemotherapy

Other: Radiotherapy
RADIOTHERAPY SCHEDULE IS DESCRIBED FOR BOTH GROUPS IN THE PERAGRAPH TITLET ARMS




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 3 years ]
    Primary aim of this study will be to compare the best response up to 36 weeks (CR+PR) between conventional and experimental irradiation. Such an end point was chosen since tumor reduction has been demonstrated to be correlated with better PFS and OS. The response will be evaluated according to radiological and clinical criteria. Radiological criteria will be RECIST ones.


Secondary Outcome Measures :
  1. disease stabilization rate [ Time Frame: 3 years ]
    the disease stabilization rates (considering only the number of patients with stable disease) will be calculated in the two treatment arms, together with the corresponding binomial 95% confidence intervals.

  2. PFS [ Time Frame: 3 years ]
    Progression-free survival (PFS) will be measured from the date of randomisation to the date of event, defined as progression or death due to any cause. Patients with no event as the time of the analysis will be censored at their last adequate tumour assessment. PFS will be estimated in the two treatment arms by the Kaplan-Meier method.

  3. OS [ Time Frame: 3 years ]
    Overall survival (OS) will be measured from the date of randomisation to the date of death due to any cause and will be censored at the date of last follow-up for patients alive at their last follow-up. OS will be estimated in the two treatment arms by the Kaplan-Meier method.

  4. radiotherapy toxicity (adverse events) [ Time Frame: 3 years ]
    The toxicity will be measured through the control of adverse events. The evaluation of adverse events will be done through the CTCAE 4.03 table.

  5. PedsQL (Paediatric Quality of Life Questionnaire) [ Time Frame: 3 years ]
    quality of life evaluation;

  6. EORTC QLQ-C30 (Quality of Life Questionnaire) [ Time Frame: 3 years ]
    quality of life evaluation

  7. Brain module (BN20) [ Time Frame: 3 years ]
    quality of life evaluation

  8. SDQ (Strength and Difficulties Questionnaire) [ Time Frame: 3 years ]
    quality of life evaluation



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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients from 2 to 21 years old will be eligible
  • No previous treatment consented apart from steroids
  • Strict eligibility criteria will radiologically-verified DIPG (an intrinsic, pontine-based infiltrative lesion hypointense on T1- and hyperintense on T2-weighted sequences, involving at least 2/3 of the pons)
  • symptoms lasting less than 6 months, life expectancy ≥4 weeks; Karnowski/Lansky performance status ≥ 40 %
  • no organ dysfunction; no pregnancy or breast-feeding
  • Patients undergo baseline cranial MRI with gadolinium, to be repeated if treatment begins more than 2 weeks; spinal MRI due to the occurrence of metastatic cases at diagnosis will also be mandatory
  • Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment.

Exclusion Criteria:

  • Patients below 2 years or over 21
  • Pre-treatment with radio or chemotherapy
  • Neurofibromatosis 1
  • Non-typical imaging
  • Symptoms duration over 6 months, Lansky/Karnowski scores below 40%
  • Metastatic disease as shown by MRI
  • Organ dysfunction, pregnancy or breast-feeding
  • Absence of parents, patient or tutor consent

Information from the National Library of Medicine

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): NCT03620032


Contacts
Contact: Maura Massimino, MD +0390223902593 maura.massimino@istitutotumori.mi.it
Contact: Iolanda Pulice +0390223903063 iolanda.pulice@istitutotumori.mi.it

Locations
Italy
Fondazione IRCCS Istituto Nazionale Tumori Recruiting
Milan, Italy, 20133
Contact: Maura Massimino, MD    +390223932593    maura.massimino@istitutotumori.mi.it   
Contact: Iolanda Pulice    +390223903063    iolanda.pulice@istitutotumori.mi.it   
Principal Investigator: Maura Massimino, MD         
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
University of Roma La Sapienza
Johannes Gutenberg University Mainz
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Wuerzburg University Hospital
Investigators
Principal Investigator: Maura Massimino, MD Fondazione IRCCS Istituto Nazionale Tumori

Publications of Results:
Memorial Sloan-Kettering Cancer Center. External beam radiation therapy and cetuximab followed by irinotecan and cetuximab for children and young adults with newly diagnosed diffuse pontine tumors and high-grade astrocytomas (POE08-01). ClinicalTrials. gov identifier NCT01012609
Fleischhack G, Siegler N, Zimmermann M, et al. Concomitant therapy of nimotuzumab and standard radiotherapy for the treatment of newly diagnosed diffuse intrinsic pontine gliomas in children and adolescents. 14th international symposium of pediatric neuro-oncology, Vienna, Austria 20-23 June 2010

Other Publications:
Bode U, Buchen S, Warmuth-Metz M, Pietsch T, Bach F, Fleischhack G. Final report of a phase II trial of nimotuzumab in the treatment of refractory and relapsed high-grade gliomas in children and adolescents [abstract]. J Clin Oncol (2007); 25(Suppl. 2006)

Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT03620032     History of Changes
Other Study ID Numbers: INT 94/15
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Antibodies, Monoclonal
Vinorelbine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents