In order to improve the survival rates and decrease progression of pancreatic advanced cancer, this study aims to evaluate the first line treatment approved for this disease (gemcitabine plus nab-paclitaxel) in combination with two experimental drugs, an inhibitor of the signaling pathway of Hedgehog and an immunotherapy drug able of blocking the CTLA-4 receptor.
Pancreatic cancer is one of the leading neoplasms in the world in terms of mortality, with very low survival rates mainly due to its rapid progression and diagnosis in advanced stages, which makes its treatment extremely difficult. Gemcitabine plus nab-paclitaxel is currently considered the first-line standard treatment for advanced pancreatic cancer due to this superiority against other treatments. In order to find an alternative to improve survival of advanced pancreatic cancer, this study aims to evaluate the efficacy with first-line treatment in combination of two experimental drugs, a Hedgehog pathway inhibitor (NLM-001) and a CTLA-4 blocker (zalifrelimab) in previously untreated patients with advanced pancreatic cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Gemcitabine 1000 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).
Nab-Paclitaxel 125 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).
NLM-001 will be administered three cycles consecutively followed by two rest cycles.
Hospital Clínico Universitario de Santiago
Santiago de Compostela, A Coruña, Spain
Hospital Universitario Virgen De La Victoria
Málaga, Andalusia, Spain
Hospital Universitario Miguel Servet
Zaragoza, Aragon, Spain
Hospital Universitario Donostia
Donostia / San Sebastian, Basque Country, Spain
Treatment efficacy according to response
Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR) according to RECIST 1.1 criteria
Time frame: 17 months
Frequency of occurrence of adverse events
Frequency of occurrence of adverse events according to NCI-CTCAE v5.0 criteria
Time frame: 8 months
Treatment efficacy according to disease control rate
Disease Control Rate (DCR): Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) evaluated by RECIST 1.1 criteria
Time frame: 8 months
Treatment efficacy according to progression free survival (PFS)
Time in months from the patient's study enrolment until patient progression according to RECIST 1.1 criteria or death.
Time frame: 8 months
Treatment efficacy according to Duration of Response (DoR)
Time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first
Time frame: 8 months
Treatment efficacy according to Overall Survival (OS)
Time in months since the patient's study enrolment until death.
Time frame: 8 months
CA 19.9
Decrease in CA 19.9 levels \> 50%
Time frame: 8 months
Gli mRNA and SMA + CAF expression and ORR
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Zalifrelimab administration each 6 weeks.
Hospital Universitari Vall d'Hebron
Barcelona, Catalonia, Spain
Hospital Universitario Marqués del Valdecilla
Santander, Spain
Correlation between change in Gli mRNA and SMA + CAF expression and Objective Response Rate (ORR).
Time frame: 1 month
Gli mRNA and SMA + CAF expression and PFS
Correlation between change in Gli mRNA and SMA + CAF expression and Progression Free Survival (PFS).
Time frame: 1 month
Collagen structure and ORR
Correlation between change in Collagen structure and Objective Response Rate (ORR)
Time frame: 1 month
Collagen structure and PFS
Correlation between change in Collagen structure and Progression Free Survival (PFS).
Time frame: 1 month
Lymphocyte infiltration and ORR
Correlation between change in lymphocyte infiltration and Objective Response Rate (ORR).
Time frame: 1 month
Lymphocyte infiltration and PFS
Correlation between change in lymphocyte infiltration and Progression Free Survival (PFS).
Time frame: 1 month