MASTER programme
Overview
- Study title: DKFZ/NCT/DKTK MASTER programme (Molecularly Aided Stratification for Tumour Eradication Research)
- Study design: Prospective, multicentre, observational study
- Study participants: Patients with rare cancer entities, locally advanced or metastasised
- Study objective: Comprehensive genetic and epigenetic analyses and derivation of treatment recommendations
- Clinical.trials.gov-Identifier / NCT-ID: NCT05852522
Study status: currently recruiting
The DKFZ/NCT/DKTK MASTER programme (Molecularly Aided Stratification for Tumour Eradication Research) is a multicentre, prospective, observational study.
It enrols patients with rare cancer entities (defined as an incidence of fewer than 6 / 100,000 per year) or rare subtypes of common cancer entities at an advanced stage of disease, regardless of whether it is a first diagnosis or a recurrence. Cancer patients with rare subtypes of a common cancer type may be included on a case-by-case basis.
As part of MASTER, comprehensive genetic and epigenetic analyses are conducted on patient material. Based on these analyses, clinically relevant therapy recommendations can be made for approximately 80 per cent of participants. In some cases, patients may be referred to suitable biomarker-based clinical trials.
Study participants are followed up with regard to therapy response, progression-free survival, and overall survival. Results from the MASTER programme to date indicate a significant improvement in progression-free survival in more than 35 per cent of study participants.
In recent years, based on the MASTER programme a steadily expanding portfolio of multicentre, academically initiated, molecularly stratified clinical trials has evolved.
If a cancer-causing germline mutation is identified, genetic counselling is offered to patient and family members. Current data suggest that this applies to approximately 10 to 14 per cent of participants.
Cancer patients can be referred to the MASTER programme via participating Comprehensive Cancer Centres or clinics at NCT- and DKTK sites. Registration is coordinated by the attending oncologist.
In addition, the MASTER programme collaborates with numerous oncologists in private practice and oncology centres, including the Centres of Excellence funded by German Cancer Aid.
MASTER is a multicentre, single-arm observational study. It includes patients with rare cancer entities or rare subtypes of common cancers and locally advanced or metastatic disease.
The MASTER programme provides comprehensive genetic and epigenetic diagnostics within a standardised and quality-controlled workflow, including:
- Whole genome sequencing (WGS) or whole exome sequencing (WES)
- RNA sequencing
- Creation of DNA methylation profiles
Aims of the MASTER programme
- Identification of not yet known therapeutic targets: Around 85 per cent of study participants receive an individual therapy recommendation.
- Identification of patients eligible for ongoing molecularly stratified clinical trials.
- Discovery of new therapeutic targets and predictive parameters (biomarkers) as a basis for future clinical trials.
Inclusion criteria
- Age ≥ 18 years
- Age < 51 years for patients with common entities, cancer patients with rare tumours may be included regardless of age
- Diagnosis of a rare cancer, or a rare subgroup of a common cancer.
- Metastatic and/or locally advanced disease with no curative treatment option available. No significant renal, haematological, or hepatic dysfunction; patient is eligible for systemic therapy.
- The patient's performance status is categorised as ≤ 2 according to the Eastern Cooperative Oncology Group (ECOG).
- Life expectancy of at least 6 months
- No concomitant renal, hepatic or haematological disease
- Availability of a suitable tissue sample (cryopreserved/unmanipulated frozen) or consent for a new biopsy
- Written informed consent from the patient
Exclusion criteria
- Patient is not suitable for the study according to the criteria above.
- Presence of a severe, uncontrolled systemic disease that poses an unacceptable risk or interferes with potential drug therapy.
- Severe neurological or psychiatric disorder that impairs the ability to provide informed consent
- Current alcohol or drug abuse
- Pregnancy or breastfeeding
1. Contacting and introducing the patient
The attending oncologist registers the patient for a study consultation by submitting a current oncology report along with complete pathological and molecular pathology findings, as well as recent imaging results (including findings from the past six months), using the contact details provided below.
An appointment will then be arranged with a study physician, during which participation is discussed and written informed consent is obtained.
2. Sampling
Tissue sample: High-throughput sequencing requires gently extracted DNA and RNA. The method of obtaining the tissue — typically via biopsy — is discussed with the patient in advance. Freshly collected native material is deep-frozen. If a biopsy is planned outside of NCT, early contact with the study team is recommended. To ensure reliable detection of molecular alterations, the tissue sample must contain at least 20 per cent tumour cells.
Blood sample: A reference blood sample is collected to identify tumour-specific alterations by comparing them with the patients’ normal genome. This sample is obtained from leucocyte DNA.
3. Molecular profiling, clinical bioinformatics
In the sample processing laboratory at NCT Heidelberg, DNA and RNA are extracted from tumour tissue, and DNA is isolated from blood samples. Sequencing is carried out at the Next Generation Sequencing Core Facility at DKFZ.
At the Computational Oncology Group within the Molecular Precision Oncology Programme of NCT Heidelberg, experts compare sequencing results from tumour and normal tissue to identify tumour-specific alterations.
All steps of sample preparation, molecular profiling, and data analysis are performed under strict quality control at the German Cancer Research Centre (DKFZ).
4. Clinical curation and interpretation of data
Based on the molecular data — and, where applicable, additional laboratory analyses such as preclinical testing of candidate agents — researchers identify potential therapeutic targets. These are matched with available approved drugs, and the likelihood of therapeutic success is assessed.
5. Molecular tumour board
Oncologists and interdisciplinary experts discuss the detected molecular alterations in a cross-site molecular tumour board. They evaluate whether a targeted therapy is appropriate based on the findings.
6. Notification of results, treatment recommendation
The study physicians inform the referring oncologist about molecular findings and, where applicable, the therapy recommendation issued by the molecular tumour board.
Together with the patient, the practitioners decide on further therapeutic steps.
7. Treatment, possibly inclusion in a clinical trial
If the patient agrees to undergo therapy based on the MASTER programme findings, cost coverage — particularly for off-label treatments — may need to be clarified with the patient’s health insurance.
Depending on the individual findings, it may also be possible to enrol the patient in a suitable clinical trial.
Patients included in MASTER are followed up with regard to their treatment outcomes, including response to therapy, progression-free survival, and overall survival.
Study Administration Office
NCT Heidelberg
Im Neuenheimer Feld 460
69120 Heidelberg
E-mail: master-at-nct-heidelberg.de
Coordinating Principal Investigator
Prof Dr Stefan Fröhling
The study is being supported by patient experts from Deutsche Sarkomstiftung e.V. and Zielgenau - Patienten-Netzwerk Personalisierte Lungenkrebstherapie e.V.
- Information page of the NCT Heidelberg on the MASTER programme
- Patient flyer of the NCT-Heidelberg
- Mock A, Teleanu MV, Kreutzfeldt S, Heilig CE, Hüllein J, Möhrmann L, Jahn A, Hanf D, Kerle IA, Singh HM, Hutter B, Uhrig S, Fröhlich M, Neumann O, Hartig A, Brückmann S, Hirsch S, Grund K, Dikow N, Lipka DB, Renner M, Bhatti IA, Apostolidis L, Schlenk RF, Schaaf CP, Stenzinger A, Schröck E, Hübschmann D, Heining C, Horak P, Glimm H, Fröhling S. NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology. NPJ Precis Oncol 7:109, 2023. doi: 10.1038/s41698-023-00458-w
- Jahn A, Rump A, Widmann TJ, Heining C, Horak P, Hutter B, Paramasivam N, Uhrig S, Gieldon L, Drukewitz S, Kübler A, Bermudez M, Hackmann K, Porrmann J, Wagner J, Arlt M, Franke M, Fischer J, Kowalzyk Z, William D, Weth V, Oster S, Fröhlich M, Hüllein J, Valle González C, Kreutzfeldt S, Mock A, Heilig CE, Lipka DB, Möhrmann L, Hanf D, Oleś M, Teleanu V, Allgäuer M, Ruhnke L, Kutz O, Knurr A, Laßmann A, Endris V, Neumann O, Penzel R, Beck K, Richter D, Winter U, Wolf S, Pfütze K, Geörg C, Meißburger B, Buchhalter I, Augustin M, Aulitzky WE, Hohenberger P, Kroiss M, Schirmacher P, Schlenk RF, Keilholz U, Klauschen F, Folprecht G, Bauer S, Siveke JT, Brandts CH, Kindler T, Boerries M, Illert AL, von Bubnoff N, Jost PJ, Metzeler KH, Bitzer M, Schulze-Osthoff K, von Kalle C, Brors B, Stenzinger A, Weichert W, Hübschmann D, Fröhling S, Glimm H, Schröck E, Klink B. Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers. Ann Oncol 33:1186-1199, 2022, doi: 10.1016/j.annonc.2022.07.008
- Horak P, Heining C, Kreutzfeldt S, Hutter B, Mock A, Hüllein J, Fröhlich M, Uhrig S, Jahn A, Rump A, Gieldon L, Möhrmann L, Hanf D, Teleanu V, Heilig CE, Lipka DB, Allgäuer M, Ruhnke L, Laßmann A, Endris V, Neumann O, Penzel R, Beck K, Richter D, Winter U, Wolf S, Pfütze K, Geörg C, Meißburger B, Buchhalter I, AugustinM, Aulitzky WE, Hohenberger P, Kroiss M, Schirmacher P, Schlenk RF, Keilholz U, Klauschen F, Folprecht G, Bauer S, Siveke JT, Brandts CH, Kindler T, Boerries M, Illert AL, von Bubnoff N, Jost PJ, Spiekermann K, Bitzer M, Schulze-Osthoff K, von Kalle C, Klink B, Brors B, Stenzinger A, Schröck E, Hübschmann D, Weichert W, Glimm H, Fröhling S. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Cancer Discov 11: 2780-2795, 2021, doi: 10.1158/2159-8290.CD-21-0126