Personalising pancreas cancer treatment: When tissue is the issue

Table 2 Ongoing biomarker directed therapy trials in pancreatic carcinoma

Trial identifier1	Name of study	Phase	Sponsor	Arms	Primary outcome	Biomarker
ACTRN12612000777897	The IMPACT trial: Individualised Molecular Pancreatic Cancer Therapy A randomised open label phase II study of standard first line treatment or personalised treatment in patients with recurrent or metastatic pancreatic cancer	II	The Australasian Gastro-Intestinal Trials Group Collaborating groups:Australian Pancreatic Cancer Genome Initiative Sydney Catalyst; the Translational Cancer Research Centre of Central Sydney and Regional NSW	Patients with actionable phenotypes randomised 1:1 to Standard -gemcitabine aloneORPersonalised Treatment -allocated based on molecular phenotype:HER2 positive sub-group - gemcitabine plus trastuzumab Homologous recombinant defects subgroup: 5FU plus MMCantiEGFR responsive sub-group: gemcitabine plus erlotinib	Progression free survival (initial pilot phase will assess feasibility of personalised approach)	Identification of actionable phenotypes based on molecular phenotype in tumour tissue in one of 3 subgroups:HER2 positive (HER2/neu amplification) subgroupHomologous recombination defects (BRCA1, BRCA2 or PALB2 mutation)AntiEGFR phenotype subgroup (KRAS wildtype or KRAS codon 13 mutation)
NCT01188109	Gemcitabine/cisplatin for resected pancreas cancer: Establishing the role of ERCC1 in treatment decision	II	Emory University	Gemcitabine and cisplatin	Progression free survival and overall survival	Immunohistochemistry, rt-PCR, and single nucleotide polymorphism assessment to determine status of ERCC1 expression and gene
NCT01488552	A Phase II study of induction consolidation and maintenance approach for patients with advanced pancreatic cancer	I/II	Pancreatic Cancer Research Team	Gemcitabine + Nab-paclitaxel inductionFOLFIRINOX consolidative Metformin + targeted agent selected by biomarkers for maintenance	Complete response rate	IHC Analysis will be performed on a fresh tissue biopsy of the tumor after chemotherapy has been administered. A targeted-based regimen will be determined from the results of the IHC analysis for the next therapy given to the patient in the maintenance phase of the study
NCT01524575	Gemcitabine and oxaliplatin in the management of metastatic pancreatic cancers with low expression of ERCC1	Phase II	University of Hawaii	Gemcitabine+oxaliplatin	6 mo overall survival	Low expression of ERCC1 protein and mRNA expression
NCT01888978	A Pilot Study of Molecularly Tailored Therapy for Patients With Metastatic Pancreatic Cancer	Phase II	Georgetown University	Gemcitabine+oxaliplatinGemcitabine + 5FUGemcitabine + docetaxelFOLFOX6Oxaliplatin + docetaxelFOLFIRIDocetaxel-irinotecan	Timing of biopsy and treatmentNumber of days from study entry to biopsy to molecular results to first dose	Selection of doublet treatment on basis of molecular analysis of tumour
NCT01585805	Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Patients With Locally Advanced or Metastatic Pancreatic Cancer	Randomised phase II	National Cancer Institute	Cisplatin+gemcitabine+/-veliparib	Optimal dose of veliparibResponse rate	BRCA1 or BRCA2 mutation carrier
NCT01586611	Study of Gemcitabine vs FOLFOX in the First Line Setting for Metastatic Pancreatic Cancer Patients Using Human Equilibrative Nucleoside Transporter 1 (hENT1) Biomarker Testing	Phase III	AHS Cancer Control Alberta	FOLFOXGemcitabine	PFS between arms in hENT1 high and hENT1 low patients	hENT1
NCT01454180	Study of Individualized Selection of Chemotherapy in Patients With Advanced Pancreatic Carcinoma According to Therapeutic Targets	Phase II	Centro Nacional de Investigaciones Oncologicas CARLOS III	Arm A: Physician discretionArm B: Therapeutic target guidedGemcitabineGemcitabine + capecitabineGemcitabine + erlotinibFOLFOXIRIFOLFOXFOLFIRI	Overall survival	Therapeutic targets expressed in tumour tissue
NCT01726582	Molecular Profiling to Guide Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma of the Pancreas	Phase II	Medical College of Wisconsin	Targeted chemotherapy prior to surgeryStandard FOLFIRINOX chemotherapy prior to surgeryGemcitabine after surgeryNo additional therapy after surgeryTargeted chemotherapy after surgeryChemoradiotherapy	Resectability rate	Molecular profile of tumour will point to particular chemotherapy treatment
				(Targeted chemotherapy include the following schedules: FOLFIRINOX, FOLFIRI, gemcitabine+irinotecan, gemcitabine + oxliplatin, gemcitabine + cisplatin, gemcitabine+nab-paclitaxel, capecitabine + nab-paclitaxel, gemcitabine, capecitabine, 5FU)

¹Trial number prefixes correspond to location of registry/portal. ANZCTRN: Australian New Zealand Clinical Trials Registry; 5FU: 5-fluorouracil; FOLFIRINOX: Fluorouracil, leucovorin, irinotecan and oxaliplatin; MMC: Mitomycin C; IHC: Immunohistochemistry; ERCC1: Excision repair cross complementation gene-1.