Table 1 Summary of clinical trials that target insulin/IGF signalling in PDAC

Kindler, H.L. et al. [86]

Metastatic pancreatic cancer

Drug 1: Placebo+Gemcitabine

Drug 2: Ganitumab (a mAb antagonist of IGF-1R) + Gemcitabine

NCT00630552

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

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

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

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

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

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

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

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

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

I

Completed

Open label

Single group assignment

To evaluate the safety and tolerability of SOM 230 LAR/Gemcitabine treatment

Treatment is well tolerated