WP15 – ProTarget: A Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on Genomic Profiling
Impact/relevance
Identification of new agents for precision medicine and identification of mechanisms of resistance. Patients undergoing whole genome sequencing (WGS) will be offered relevant targeted agents according to molecular tumor board review. The study aims to catalogue the choice of genomic test by clinical oncologists and learn about the utility of data collected through this study to develop hypotheses for future clinical trials.
Background
Our deeper understanding of cancer at the genomic level, coupled with the increasingly widespread availability of affordable technologies to interrogate the genome, the transcriptome, the proteome and other aspects of the tumor and host is leading to new paradigms of cancer care that rely increasingly on tumor molecular profiling throughout the course of care to refine prognosis and inform treatment decisions 1-4.
A new generation of drugs, both antibodies and small molecules, that target specific molecules and pathways crucial for cancer survival or progression, has revolutionized the treatment of some cancers and given hope to many patients with cancers once considered hopeless.
ProTarget study is based on the study protocols of the Dutch DRUP trial and the TAPUR trial sponsored by ASCO in the US. ProTarget study is a phase II, prospective, non-randomized investigator-initiated clinical trial that aims to describe the safety and efficacy of commercially available, targeted anti-cancer drugs prescribed for treatment of patients with advanced cancer having a potentially actionable genomic variant revealed by a genomic test or immunohistochemistry test for protein overexpression performed in a laboratory accredited by the competent local regulatory authority. Supplementary WGS will be performed for all patients for translational research.
Aims
-To describe in different types of population the anti-tumour activity (efficacy) and toxicity (safety) of commercially available, targeted anti-cancer drugs used for treatment of patients with advanced disease with a genomic variant known (i) to be a target of an EMA-approved anti-cancer drug or (ii) to predict sensitivity to an EMA-approved anti-cancer drug.
-To record the site investigator determines treatment-related adverse events experienced by patients receiving treatment with commercially available, targeted anti-cancer drugs.
-To perform refined biomarker analyses, including (but not limited to) whole genome sequencing, on a fresh tumour biopsy specimen at baseline and at progression.
Methods
Each patient will be allocated to open cohorts at the weekly national Molecular Tumour Board. At present time 12 drugs are provided free of charge by pharma companies. All patients who receive treatment with a drug available in the protocol will be followed for standard toxicity and efficacy outcomes including tumour response, progression-free and overall survival as well as duration of treatment and high grade or serious adverse events.
Expected outcome
Assessment of response rates and 6 months disease-free survival (DFS), safety and resistance mechanisms for various targeted agents in GBM and other tumors types.
References
1. MacConaill, L.E., Garraway, L.A.: Clinical Implications of the Cancer Genome. J Clin Oncol. 28: 5219-5228, 2010.
2. Garraway, L.A.: Genomics-Driven Oncology: Framework for an Emerging Paradigm. J Clin Oncol. 31: 1806-1814, 2013.
3. Dienstmann, R., Rodon, J., Barretina, J., Tabernero, J.: Genomic Medicine Frontier in Human Solid Tumors: Prospect Challenges. J Clin Oncol. 31: 1874-1884, 2013.
4. Meador, C.B., Micheel, C.M., Levy, M.A., Lovly, C.M., Horn, L., Warner, J.L., Johnson, D.B., Zhao, Z., Anderson, I.A., Sosman, J.A., Vnencak-Jones, C.L., Dahlman, K.B., Pao, W.: Beyond Histology: Translating Tumor Genotypes into Clinically Effective Targeted Therapies. Clin Cancer Res. 20: 2264, 2014.
Travel Grant
We are happy to announce Laila Belcaid, MD, PhD student (WP 15 ProTarget), in September 2021 received a Travel Grant, a donation of DKK 73.120 from The NEYE Foundation in support of her research at the Institute Gustave Roussy , France. The purpose of the donation is to change of the research environment at the Institute Gustave Roussy, to enhance the international collaboration in personalized cancer medicine.