NCT Neuro Master Match - N²M² (NOA-20)

NCT03158389 | Completed Phase 1 DMC

• 2 other identifiers: NCT-2014-0235/N2M22015-002752-27
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 13

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.

Conditions

Glioblastoma, Adult

Keywords

MGMT methylation; targeted therapy; umbrella protocol

Outcome Measures

Primary Outcomes (1)

• PFS-6 rate

  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.

  6 months

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (AE)

  6 months

• Overall survival (OS)

  6 months

Study Arms (7)

Subtrial A: APG101

EXPERIMENTAL

* weekly application of 800 mg i.v. for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: APG101

Subtrial B: Alectinib

EXPERIMENTAL

* 600 mg orally twice daily (bid) for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: Alectinib

Subtrial C: Idasanutlin

EXPERIMENTAL

* at escalating doses from 100 mg until maximum tolerated dose daily administered (orally) on five consecutive days of a 28-day cycle for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: Idasanutlin

Subtrial D: Atezolizumab

EXPERIMENTAL

* application of 1200 mg i.v. every three weeks for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: Atezolizumab

Subtrial E: Vismodegib

EXPERIMENTAL

* daily application of 150 mg orally for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: Vismodegib

Subtrial F: Palbociclib

EXPERIMENTAL

* 75/100/125 mg orally once daily on 21/28 days * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks * followed by a 4 weeks break (after last dose of 2nd cycle) * and with maintenance therapy with palbociclib at 125 mg daily for 6 months or until progression

Drug: Palbociclib

Subtrial G: Temsirolimus

EXPERIMENTAL

* weekly application of 25 mg i.v. for 6 months or until progression * in conjunction with radiotherapy (at 60 Gy in 2 Gy fractions) for the first 6 weeks

Drug: Temsirolimus

Interventions

APG101 DRUG

weekly i.v.

Subtrial A: APG101

Alectinib DRUG

twice daily (oral)

Also known as: Alecensa

Subtrial B: Alectinib

Idasanutlin DRUG

orally on 5 days of a 28 days cycle

Subtrial C: Idasanutlin

Atezolizumab DRUG

i.v. every 3 weeks

Subtrial D: Atezolizumab

Vismodegib DRUG

daily orally

Also known as: Erivedge

Subtrial E: Vismodegib

Temsirolimus DRUG

weekly i.v.

Also known as: Troisel

Subtrial G: Temsirolimus

Palbociclib DRUG

orally on 21 days of a 28 days cycle

Also known as: Ibrance

Subtrial F: Palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, methylation 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 ≤ 72 (+ 12 h) post-surgery according to the present national and international guidelines
• Availability of fresh-frozen tissue, formalin-fixed, paraffin-embedded (FFPE) tissue, and blood
• Patients eligible for RT at 60 Gy in 2 Gy fractions according to the local Standard of Care
• 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.

You may not qualify if:

• Abnormal (≥ Grade 2 CTCAE v5.0) 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

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• German Cancer Aid: collaborator
• German Cancer Research Center: collaborator
• National Center for Tumor Diseases, Heidelberg: collaborator

Study Sites (13)

Charité Berlin, Neurosurgery

Berlin, Germany

Location

Knappschaftskrankenhaus Bochum GmbH, Neurology Clinic

Bochum, Germany

Location

University Hospital Bonn, Neurology Clinic

Bonn, Germany

Location

University Hospital Cologne, Neurosurgery

Cologne, Germany

Location

University Hospital Dresden, Neurosurgery

Dresden, Germany

Location

University Hospital Essen, Neurology Clinic

Essen, Germany

Location

University Hospital Frankfurt, Neurooncology

Frankfurt am Main, Germany

Location

University Hospital Heidelberg, Neurology Clinic

Heidelberg, Germany

Location

University Hospital Saarland, Neurosurgery

Homburg, Germany

Location

University Hospital Mainz, Neurosurgery

Mainz, Germany

Location

University Hospital Mannheim, Neurology Clinic

Mannheim, Germany

Location

University Hospital Regensburg, Neurology Clinic

Regensburg, Germany

Location

University Hospital Tuebingen, Neurooncology

Tübingen, Germany

Location

Related Publications (1)

• Wick W, Lanz LM, Wick A, Harting I, Dettmer S, Suwala AK, Ketter R, Tabatabai G, Seliger C, Glas M, Burger MC, Timmer M, Ringel FA, Mildenberger I, Schulz-Schaeffer WJ, Winkler F, Konig L, Herold-Mende C, Eisenmenger A, Pfister SM, Renovanz M, Bendszus M, Sahm F, Platten M, Kessler T. Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial. Nat Med. 2025 Oct;31(10):3534-3541. doi: 10.1038/s41591-025-03928-9. Epub 2025 Sep 5.

  PMID: 40913172 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

APG101; alectinib; RG7388; atezolizumab; HhAntag691; temsirolimus; palbociclib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Wolfgang Wick, Prof. Dr.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: May 7, 2018
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (13)