The ProTarget study – A Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on Genomic Profiling

Precision oncology is generally defined as a strategy that aims to identify the most beneficial treatment for each individual patient based on the molecular profile of the patient’s tumor. The strategy uses extensive genome sequencing-data and biomarker testing to identify druggable alterations, and potential resistance variants, to tailor the most optimal treatment plan that may improve survival and quality of life for each patient.

The ProTarget study is a Danish investigator-initiated phase 2, prospective, non-randomized clinical trial. ProTarget aims to facilitate patient access to commercially available molecularly targeted anti-cancer drugs based on genomic profiling and further aims to investigate the safety and efficacy when these treatments are used off-label.

Patients, who are eligible for treatment in ProTarget, have an advanced cancer disease and have exhausted all standard treatments. They must have at least one of the predefined, potentially druggable genomic alterations and the cancer disease cannot be within the labeled indication for the molecularly matched drug. The trial aims to include 100 patients per year.

The ProTarget study has multiple treatments available, which are all EMA- and FDA-approved, including inhibitors targeting ALK/RET, BRAF/MEK, ERBB2, VEGFR1-3, EGFR, PARP, and FGFR, as well as immune checkpoint inhibitors, and more drugs are in the pipeline. All patients with a drug-match must be discussed and confirmed on the Danish National Tumor Board before inclusion in the trial.

Primary endpoints are:

  • Anti-tumor activity, as assessed by objective response, at 16 weeks
  • Stable disease at 16 weeks
  • Treatment-related and serious adverse events

Secondary study endpoints are:

  • Duration of response, progression-free and overall survival
  • Duration of treatment on study (time on drug)
  • Percentage of screened patients treated based on their molecular tumor profile

Exploratory study endpoints include:

  • Description of concordance between mutational profile of pre-treatment tumor biopsies and mutational profile according to tumor profiling tests that were used to enroll patients
  • Identification of patterns of resistance based on serial tumor biopsies and liquid biopsies

Serial tumor and liquid biopsies (circulating tumor DNA) are collected for extensive translational research and will be analyzed using techniques such as whole-genome sequencing, whole-genome array, and RNA sequencing. The trial thereby aims to identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance to targeted therapies.

The trial opened in August 2020 and include sites at Rigshospitalet, Herlev Hospital, Zealand University Hospital, Odense University Hospital, Vejle Hospital, Aarhus University Hospital, Regional Hospital Goedstrup, and Aalborg University Hospital. The ProTarget trial coordinating team is situated at Rigshospitalet, Denmark. The trial is monitored by the Danish GCP Units.

The ProTarget trial collaborate with other Nordic and European trials of similar design e.g., by sharing cohorts, which will ensure the completion of cohorts containing rare genomic profiles and increase the power of the results.

Link: https://clinicaltrials.gov/ct2/show/NCT04341181



Sponsor and trial coordinating team

Ulrik Lassen
Sponsor and Study Principal Investigator

Tina Kringelbach
Trial Coordinator

Kristina Vile Jensen
Research Coordinator

Study sites and Principal Investigators

Principal Investigator, Kristoffer Rohrberg
Site is open and recruiting

Aarhus University Hospital
Principal Investigator, Britt Elmedal Laursen
Site is open and recruiting

Zealand University Hospital
Principal Investigator, Julie Gehl
Site is open and recruiting

Aalborg University Hospital
Principal Investigator, Morten Ladekarl
Site is open and recruiting

Herlev Hospital
Principal Investigator, Rikke Eefsen
Site is open and recruiting

Odense University Hospital
Principal Investigator, Karin Holmskov
Site is open and recruiting

Vejle Sygehus
Principal Investigator, Lars Henrik Jensen
Site is open and recruiting

Principal Investigator, Trine H. Oellegaard
Site is open and recruiting