Table 5.

Clinical studies related to the tumor microenvironment of pancreatic cancer between 2011 and 2021.

Study	ClinicalTrials.gov Identifier	Official title	Time	Country	Design	No. of patients	Conditions	Intervention		Phase	Primary purpose	Summary
								Treatment group	Comparison group
1	NCT03331562	A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer	2017.12.27-2020.06.29	Germany	Randomized, Parallel Assignment, Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)	24	Pancreatic Cancer, Pancreas Adenocarcinoma, Advanced Pancreatic Cancer, Metastatic Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma	Drug: Pembrolizumab, Drug: paricalcitol	Drug: placebo	Phase 2	Treatment	The study is being conducted to determine the effects that pembrolizumab, with or without the addition of paricalcitol, may have on pancreatic cancer. Half of the patients will be randomized to receive pembrolizumab + paricalcitol and half to receive pembrolizumab + placebo.
2	NCT03168139	Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer	2017.04.18-2020.03.25	Germany	N/A, Single Group Assignment, None (Open Label)	20	Metastatic Colorectal Cancer, Metastatic Pancreatic Cancer	Drug: Olaptesed pegol - Monotherapy, Drug: Olaptesed pegol + Pembrolizumab - Combination Therapy	NO	Phase 1	Treatment	The purpose of this study is to show that the type, number and/or distribution of tumor metastases infiltrating immune cells such as cytotoxic T cells and/or the cytokine signature in the tumor metastases can be modulated by treatment with olaptesed pegol and to explore safety, tolerability and efficacy of olaptesed pegol in combination with pembrolizumab as a basis for subsequent studies in combination with immunotherapies, in particular checkpoint inhibitors.
										Phase 2
3	NCT02777710	Evaluation of Safety and Activity of an Anti-PDL1 Antibody (DURVALUMAB) Combined With CSF-1R TKI (PEXIDARTINIB) in Patients With Metastatic/Advanced Pancreatic or Colorectal Cancers	2016.06-2019.11	France	N/A, Single Group Assignment, None (Open Label)	48	Colorectal Cancer, Pancreatic Cancer, Metastatic Cancer, Advanced Cancer	Drug: Pexidartinib, Drug: Durvalumab	NO	Phase 1	Treatment	The study is to conduct a Phase I dose escalation study in order to evaluate the safety and clinical activity of a combined treatment associating an anti-CSF1R (PEXIDARTINIB) with an anti-PD-L1 (DURVALUMAB) in patients with advanced/metastatic colorectal or pancreatic cancers. Dose escalation part will determine the Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Pexidartinib given in combination with Durvalumab. Extension part will evaluate the clinical activity of the combination at the RP2D.
4	NCT02179970	To Assess the Safety of Continuous IV Administration of Plerixafor in Patients With Advanced Pancreatic, Ovarian and Colorectal Cancers	2015.06-2018.12.14	France	N/A, Single Group Assignment, None (Open Label)	26	Pancreatic Adenocarcinoma Metastatic, Ovarian Serous Adenocarcinoma, Colorectal Cancer Metastatic	Drug: Plerixafor	NO	Phase 1	Treatment	The purpose of this study is to find out if the study drug has the same effect on patients with advanced pancreatic, ovarian or colorectal cancer, as they have seen in our laboratory experiments, and find out the right dose of the study drug to give.
5	NCT02030860	A Randomized Pilot/Pharmacodynamic/Genomic Study of Neoadjuvant Paricalcitol to Target the Microenvironment in Resectable Pancreatic Cancer	2014.01-2015.12	USA	Randomized, Parallel Assignment, None (Open Label)	15	Adenocarcinoma of the Pancreas	Drug: Paricalcitol, Drug: Abraxane, Drug: Gemcitabine	NO	Not Applicable	Treatment	This study is a randomized pilot/pharmacodynamic/genomic study of neoadjuvant paricalcitol to target the microenvironment in resectable pancreatic cancer to determine the effect of targeting the vitamin D metabolic program in the tumors of patients treated with one cycle of gemcitabine/abraxane with or without paricalcitol prior to surgery for resectable pancreatic cancer through an assessment of cellular and imaging markers.
6	NCT01989000	The Role of the Tumor Microenvironment of Pancreatic Cancer to Predict Treatment Outcome	2013.11-2017.12	Netherlands	Nonrandomized, Parallel Assignment, None (Open Label)	47	Pancreatic Cancer	Drug: Gadobutrol, Drug: [F-18]HX4, Drug: Gemcitabine, Radiation: Radiotherapy, Procedure: Pancreaticoduodenectomy	NO	Not Applicable	Diagnostic	The study is to use tumor cellularity and extracellular matrix composition to assess non-invasively in vivo by diffusion weighted magnetic resonance imaging (DWI) and tumor vascularity can be assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Tumor hypoxia can be evaluated by T2* MRI and PET-CT, using the 18F-labeled hypoxic marker HX4.
7	NCT01903083	Chemoimmunotherapy and Radiation in Pancreatic Cancer	2013.07-2017.12	USA	N/A, Single Group Assignment, None (Open Label)	10	Locally Advanced Malignant Neoplasm	Drug: Tadalafil, Drug: Gemcitabine, Radiation: Radiation, Procedure: Pancreaticoduodenectomy	NO	Phase 1	Treatment	The goal of this study is to evaluate the safety of combination treatment that includes chemotherapy, radiation therapy, and immunotherapy in patients with pancreatic cancer.
8	NCT01715142	Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Pancreatic Cancer	2013.03.21-2015.09.21	USA	N/A, Single Group Assignment, None (Open Label)	23	Pancreatic Adenocarcinoma Resectable, Pancreatic Adenocarcinoma Locally Advanced, Pancreatic Adenocarcinoma Metastatic.	Drug: Gemcitabine, Drug: Abraxane	NO	Early Phase 1	Treatment	This proof-of-concept trial is studying the “dynamic” tumor response after the administration of a short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4 weeks = 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer (cohort 2 = 10 patients).
9	NCT02546531	Defactinib Combined With Pembrolizumab and Gemcitabine in Patients With Advanced Cancer	2015.09-2021.05	USA	Nonrandomized, Parallel Assignment, None (Open Label)	43	Pancreatic Cancer	Drug: Gemcitabine Drug: Defactinib Drug: Pembrolizumab	NO	Phase 1	Treatment	Focal adhesion kinase (FAK) inhibitors have demonstrated reasonable anti-tumor activity in the preclinical setting. A maximal synergetic effect was achieved when a FAK inhibitor was given in combination with a PD-1 antagonist and chemotherapy in multiple pancreas tumor animal models. This supports the concept of using FAK inhibitors to reduce stromal fibrosis during checkpoint immunotherapeutic treatment. Therefore, these robust preclinical findings will be tested in the proposed phase I trial.