Background
Tumor cell-intrinsic effects of IGF signaling in PDAC
IGF signaling in the PDAC stroma
Activated stromal (myo-) fibroblasts as a leading source of IGF-1 in PDAC
Control of IGFBP levels by stromal proteases
Regulation of anti-tumor immunity in PDAC stroma by IGF signaling
Hyperinsulinemia promotes stromal activation and fibrosis in PDAC
Impact on the exocrine-endocrine crosstalk in PDAC
The impact of insulin/IGF-1R signaling on chemotherapy and targeted therapies in PDAC: current and novel directions
Author/Principal investigators | Malignancy | Treatment | NCT accession number | Enrollment number | Phase | Status | Study type | Primary outcome/objectives | Summary of results |
---|---|---|---|---|---|---|---|---|---|
Kindler, H.L. et al. [86] | Metastatic pancreatic cancer | Drug 1: Placebo+Gemcitabine Drug 2: Ganitumab (a mAb antagonist of IGF-1R) + Gemcitabine | NCT00630552 | 42 | II | Completed | Randomized Open label Placebo controlled | To evaluate the efficacy and safety of Ganitumab/ Gemcitabine treatment in patients with metastatic pancreatic cancer | A slight improvement in 6-month survival rate in patients who are treated with Ganitumab/Gemcitabine compared to the patients who have received Gemcitabine monotherapy has been observed |
Fuchs, C.S. et al. [82] | Metastatic pancreatic adenocarcinoma | Drug 1: Placebo+Gemcitabine Drug 2: Ganitumab+Gemcitabine | NCT01231347 | 825 | III | Terminated | Randomized Double blind Placebo controlled Multicenter | To evaluate the efficacy and safety of Ganitumab/Gemcitabine in first-line treatment of metastatic pancreatic adenocarcinoma | No improvement in the survival rate of patients that are treated with Ganitumab/Gemcitabine compared to the patients that received Gemcitabine monotherapy |
Tabernero, J. et al. [87] | Advanced, refractory solid tumours including pancreatic cancer | Drug 1: Ganitumab Drug 2: Conatumumab. (mAb that binds to DR5) | NCT00819169 | 89 | Ib-II | Terminated | Non-randomized Open label Parallel assignment | Phase Ib: To determine the dose of Ganitumab/Conatumumab treatment. Phase II: To evaluate the efficacy of the combined Ganitumab/ Conatumumab treatment in the patients with pancreatic, lung, colorectal, ovarian cancers and sarcoma | Ganitumab/Conatumumab treatment is safe to apply but has no effects on survival rate of patients in the tested population |
Philip, P.A et al. [88] | Stage IV pancreatic cancer | Drug 1: Cixutumumab (mAb antagonist of IGF-1R) Drug 2: Erlotinib (EGFR Inhibitor) Drug 3: Gemcitabine | NCT00617708 | 134 | Ib-II | Completed | Randomized Open label Parallel assignment | Phase Ib: To determine the dose of Cixutumumab to be used in combination with Erlotinib/Gemcitabine Phase II: To evaluate the efficacy of Cixutumumab/ Erlotinib/ Gemcitabine in patients with pancreatic cancer | No difference in progression free survival of patients who received Cixutumumab/Erlotinib/Gemcitabine treatment compared to the patients that are treated with Erlotinib/Gemcitabine |
Javle, M. et al. | Pancreatic adenocarcinoma | Drug 1: MK-0646 (Dalotuzumab- mAb, IGF-1R antagonist) Drug 2: Gemcitabine Drug 3: Erlotinib | NCT00769483 | 100 | I-II | On-going, not recruiting participants | Randomized Open label Parallel assignment | Phase I: To determine the ‘maximum tolerated dose (MTD)’ of MK-0646/ Gemcitabine, MK-0646/ Gemcitabine/Erlotinib and Gemcitabine/Erlotinib combined therapy Phase II: To evaluate the ‘progression free survival’ under the three-different therapies with the MTD determined in Phase I | Results are expected by November 2018 |
Braghiroli, M.I. et al. [89] | Advanced metastatic pancreatic cancer | Drug 1: Paclitaxel Drug 2: Metformin | NCT01971034 | 41 | II | Completed | Open label Single group assignment | To evaluate efficacy of Metformin/Paclitaxel treatment compared to the standard Paclitaxel monotherapy | Combined therapy was poorly tolerated by patients and did not improve state of the disease in patients |
Renouf, D.J. (British Columbia Cancer Agency) | Respectable PDAC | Drug 1: Metformin | NCT02978547 | 20 | II | On-going, not open yet to recruit participants | Open label Single group assignment | To evaluate the effect of neoadjuvant metformin treatment on tumor cell growth | Results are expected by January 2019 |
Merrimack Pharmaceuticals | Metastatic pancreatic adenocarcinoma | Drug 1: MM-141 Drug 2: Placebo Drug 3: Gemcitabine Drug 4: Nab-Paclitaxel | NCT02399137 | 260 | II | On-going, recruiting participants | Randomized Double blind Placebo control Parallel assignment | To evaluate the efficiency of MM-141/Nab-Paclitaxel/Gemcitabine combined therapy compared to the Nab-Paclitaxel/Gemcitabine therapy | Results are expected by November 2018 |
Yeh, J. (John Hopkins University) | Solid tumors including pancreatic cancer | Drug 1: Metformin Behavioral 1: Coach-directed behavioral weight loss Behavioral 2: Self-control weight loss | NCT02431676 | 120 | II | On-going, recruiting participants | Randomized Single blind Parallel assignment | To evaluate the IGF-1 levels and IGF-1/IGFBP-3 ratio in the serum of participants within the next 6 and 12 months survival after surgery. | Results are expected by June 2018 |
Suleiman, Y. et al. [90] | Advanced or metastatic pancreatic cancer | Drug 1: SOM 230 LAR (somatostatin agonist and potent IGF-1R inhibitor) Drug 2: Gemcitabine | NCT01385956 | 20 | I | Completed | Open label Single group assignment | To evaluate the safety and tolerability of SOM 230 LAR/Gemcitabine treatment | Treatment is well tolerated |