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NCT Neuro Master Match - N²M² (NOA-20) (N²M²)

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ClinicalTrials.gov Identifier: NCT03158389
Recruitment Status : Recruiting
First Posted : May 18, 2017
Last Update Posted : May 17, 2018
Sponsor:
Collaborators:
German Cancer Aid
German Cancer Research Center
National Center for Tumor Diseases, Heidelberg
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Wick, University Hospital Heidelberg

Brief Summary:
The objective of N²M² is the improvement of overall survival of patients with glioblastoma with an unmethylated MGMT promoter based on molecular characterization and use of targeted compounds in a modern trial design. The progression-free survival rate at six months (PFS-6) will be used to make decisions.

Condition or disease Intervention/treatment Phase
Glioblastoma, Adult Drug: APG101 Drug: Alectinib Drug: Idasanutlin Drug: Atezolizumab Drug: Vismodegib Drug: Temsirolimus Drug: Palbociclib Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Umbrella Protocol for Phase I/IIa Trials of Molecularly Matched Targeted Therapies Plus Radiotherapy in Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Methylation: NCT Neuro Master Match - N²M² (NOA-20)
Actual Study Start Date : May 7, 2018
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Subtrial A: APG101
  • weekly application of 400/600/800 mg i.v. until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: APG101
weekly i.v.

Experimental: Subtrial B: Alectinib
  • 600 mg orally twice daily (bid) for 6 until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: Alectinib
twice daily
Other Name: Alecensa

Experimental: Subtrial C: Idasanutlin
  • at escalating doses from 100 mg until maximum tolerated dose daily administered (orally) on five consecutive days of a 28-day cycle until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: Idasanutlin
on 5 days of a 28 days cycle

Experimental: Subtrial D: Atezolizumab
  • application of 1200 mg i.v. every three weeks until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: Atezolizumab
i.v. every 3 weeks

Experimental: Subtrial E: Vismodegib
  • daily application of 150 mg orally until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: Vismodegib
daily orally
Other Name: Erivedge

Experimental: Subtrial F: Palbociclib
  • 75/100/125 mg orally once daily on 21/28 days
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions)
  • followed by a 4 weeks break (after last dose of 2nd cycle)
  • and with maintenance therapy with palbociclib at 125 mg daily until progression
Drug: Palbociclib
orally on 21 days of a 28 days cycle
Other Name: Ibrance

Experimental: Subtrial G: Temsirolimus
  • weekly application of 25 mg i.v. until progression
  • in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks
Drug: Temsirolimus
weekly i.v.
Other Name: Troisel




Primary Outcome Measures :
  1. PFS-6 rate [ Time Frame: 6 months ]
    defined as the proportion of patients free of progression at 6 months after study entry. PFS will be calculated from study entry until clinical or radiographic progression or death, whichever comes first.Progression will be evaluated according to Response Assessment in Neurooncology (RANO) criteria or Immunotherapy Response Assessment in Neurooncology (iRANO) criteria.


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (AE) [ Time Frame: 6 months ]
    Toxic effects will be graded according to CTCAE v4.03.

  2. Overall survival (OS) [ Time Frame: 6 months ]
    defined as the time from first administration of the investigational medicinal product (IMP) to time of death from any cause.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Histologically confirmed, newly diagnosed glioblastoma (astrocytoma World Health Organization (WHO) grade IV) with unmethylated MGMT promoter determined by one of the accepted methods (qPCR, pyrosequencing, 450k array) and without mutation of the isocitrate dehydrogenase genes
  • Open biopsy or resection
  • Craniotomy or intracranial biopsy site must be adequately healed
  • Informed consent
  • Standard MRI ≤ 48 (+ 6 h) post-surgery according to the present national and international guidelines
  • Availability of fresh-frozen tissue, formalin-fixed, paraffin-embedded (FFPE) tissue, and blood
  • Age: ≥18 years
  • Karnofsky performance status (KPS) ≥70%
  • Life expectancy > 6 months
  • All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 6 days prior to start of therapy. All female patients must be surgically sterile or must agree to use adequate contraception during the period of therapy and 6 months after the end of study treatment, or women must be postmenopausal for at least 2 years. Acceptable methods of contraception comprise barrier contraception combined with a medically accepted contraceptive method for the female patient (e.g. intra-uterine device with spermicide, hormonal contraceptive since at least 2 month). Female patients must agree not to donate lactation during treatment and until 6 months after end of treatment
  • Male patients willing to use contraception (condoms with spermicidal jellies or cream) upon study entry and during the course of the study and 3 months after the end of the study, have undergone vasectomy, or are practicing total abstinence. Sperm donation is not permitted for the same time interval.

Main Exclusion Criteria:

  • Abnormal (≥ Grade 2 CTCAE v4.03) laboratory values for hematology, liver or renal function.
  • HIV infection or active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue (e.g. rabies).
  • Prior therapy for glioma (except surgery and steroids) including but not limited to carmustine wafers and immunotherapy.
  • Concurrent participation in another interventional clinical trial studying a drug or treatment regimen.
  • Insufficient tumor material for molecular diagnostics
  • Pregnant and lactating women
  • History of hypersensitivity to any of the additives of the study drug formulations
  • Co-administration of anti-cancer therapies other than those administered/allowed in this study
  • Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study
  • Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry

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): NCT03158389


Contacts
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Contact: Wolfgang Wick, Prof. Dr. +49 (0)6221 56 ext 7075 wolfgang.wick@med.uni-heidelberg.de

Locations
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Germany
Charité Berlin, Neurosurgery Not yet recruiting
Berlin, Germany
Knappschaftskrankenhaus Bochum GmbH, Neurology Clinic Not yet recruiting
Bochum, Germany
University Hospital Bonn, Neurology Clinic Not yet recruiting
Bonn, Germany
University Hospital Cologne, Neurosurgery Not yet recruiting
Cologne, Germany
University Hospital Dresden, Neurosurgery Not yet recruiting
Dresden, Germany
University Hospital Essen, Neurology Clinic Not yet recruiting
Essen, Germany
University Hospital Frankfurt, Neurooncology Not yet recruiting
Frankfurt am Main, Germany
University Hospital Heidelberg, Neurology Clinic Recruiting
Heidelberg, Germany
University Hospital Saarland, Neurosurgery Not yet recruiting
Homburg, Germany
University Hospital Mainz, Neurosurgery Not yet recruiting
Mainz, Germany
University Hospital Mannheim, Neurology Clinic Not yet recruiting
Mannheim, Germany
University Hospital Regensburg, Neurology Clinic Not yet recruiting
Regensburg, Germany
University Hospital Tuebingen, Neurooncology Not yet recruiting
Tübingen, Germany
Sponsors and Collaborators
University Hospital Heidelberg
German Cancer Aid
German Cancer Research Center
National Center for Tumor Diseases, Heidelberg
Investigators
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Principal Investigator: Wolfgang Wick, Prof. Dr. University Hospital Heidelberg

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Responsible Party: Prof. Dr. Wolfgang Wick, Coordinating Investigator, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT03158389     History of Changes
Other Study ID Numbers: NCT-2014-0235/N2M2
2015-002752-27 ( EudraCT Number )
First Posted: May 18, 2017    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Prof. Dr. Wolfgang Wick, University Hospital Heidelberg:
MGMT methylation
targeted therapy
umbrella protocol

Additional relevant MeSH terms:
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Atezolizumab
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Palbociclib
Everolimus
Sirolimus
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents