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2023-06-14
2024-12-23
2024-12-23
0
NCT05861336
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
INTERVENTIONAL
GEM+Nab-Paclitaxel Plus Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer
Single-arm, prospective, phase II study to evaluate safety and activity of an induction therapy with Gemcitabine (GEM) and nab-paclitaxel plus Losartan followed by Stereotactic Radiotherapy (SBRT) in patients affected by Locally Advanced Pancreatic Cancer (LAPC).
Pancreatic cancer (PC) is a malignant disease presenting high mortality rates, with a 5-year survival of about 11%, partly because of its known resistance to Chemotherapy (CHT) and Radiotherapy (RT). Radiation therapy in locally advanced and borderline resectable pancreatic cancer improves only local control as demonstrated by 5 studies published from 1980 to 2011 and confirmed by the more recent LAP-07 trial, which investigated conventional RT after induction CHT with the same results. Losartan was administered because it indirectly affects tumor microenvironment mechanisms of chemo- and radioresistance. PC cells, through transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF) and Angiotensin II activating signaling pathways lead to tumor microenvironment (TME) cells activation, like pancreatic stellate cells, which play a key role in chemoresistance. Angiotensin system and TGF-β increase and maintain the extracellular matrix, which acts as a barrier against drugs. Murphy et al. showed that Losartan administration during chemotherapy resulted in an effective decrease in plasma levels of TGF-β. Their unexpected successful results suggest that targeting not only tumor but also TME might be a novel treatment paradigm. The purpose of this study is to prospectively evaluate the safety and activity, in terms of resectability rate, of GEM-nab-paclitaxel chemotherapy with concurrent Losartan followed by SBRT in patients with LAPC. Secondary endpoints are margin-negative resection rate (R0), progression-free survival (PFS), overall survival (OS), blood biomarkers response, safety and quality of life. A Carbohydrate antigen-19.9 (CA19.9) reduction ≥15% from baseline to the end of induction therapy and Carcinoma embryonic antigen (CEA) are tested as a reliable prognostic factor.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2023-03-21 | N/A | 2024-12-23 |
2023-05-12 | N/A | 2024-12-27 |
2023-05-16 | N/A | 2024-12 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Na
Interventional Model:
Single Group
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Chemotherapy+Losartan+Stereotactic Radiation Chemotherapy will be administered for six cycles as per clinical practice (nab-paclitaxel and gemcitabine: nab-paclitaxel 125 mg/m2 on days 1, 8, and 15, Gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days) Losartan will be administered per os every | DRUG: Losartan
DRUG: Gemcitabine
DRUG: Nab paclitaxel
RADIATION: Stereotactic Body Radiation Therapy
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Number of participants discontinuing study treatment due to treatment related grade≥3 non-hematological adverse event [Toxicity] | Toxicity-related discontinuation is defined as: for chemotherapy + losartan phase, discontinuation due to a treatment-related ≥grade3 non-hematological adverse event; Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0. | 40 months |
| Number of participants discontinuing study treatment due to treatment related grade≥3 adverse event [Toxicity] | Toxicity-related discontinuation is defined as: for SBRT phase, discontinuation due to a ≥grade3 Adverse Events (Enteritis, Gastritis, Malabsorption, Nausea) occurring for three consecutive days. Toxicity assessments will be done using the NCI Common Terminology Criteria for Adverse Events v 5.0. | 40 months |
| Resectability rate | Rate of patients undergoing surgery on total patient population. Resectability will be determined by Multidisciplinary team according | 40 months |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| margin-negative resection rate (R0) | Rate of negative margin resection determined by final pathology of the surgical specimen | 80 months |
| progression-free survival (PFS) | Progression-free survival will be defined as the time from the start date of protocol therapy to first objective documentation of progressive disease (distant or local) or death due to any cause or last tumor evaluation | 80 months |
| overall survival (OS) | Overall survival will be calculated as the time from the start date of protocol therapy to date of death due to any cause or last follow-up | 80 months |
| biomarker blood response | A CA19.9 reduction ≥15% from baseline to the end of induction therapy and CEA are tested as a reliable prognostic factor | 80 months |
| Incidence of Treatment-Emergent Adverse Events [Toxicity] | All patient will be evaluated for toxicity using the NCI Common Terminology Criteria for Adverse Events (CTCAE v 5.0). All patients will be evaluated for toxicity after each therapy session. Toxicity analyses will be performed on all patients who received at least one dose of study treatment. Frequency tables will be performed for all categorical variables. Continuous variables will be presented using the median and range. | 80 months |
| Quality of life questionnaire (QLQ) | Quality of Life will be measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire that is a patient-reported outcome measure used to assess health-related quality of life in patients undergoing cancer therapy. The scale ranging from 1-4, where 1 is labeled 'Good quality of life,' and 4 is labeled 'Bad quality of life'. | 80 months |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
NPCF was founded on May 29, 2009 and is a 501(c)(3) organization. All donations are tax deductible.
The information and services provided by the National Pancreatic Cancer Foundation are for informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnosis or treatment. The National Pancreatic Cancer Foundation does not recommend nor endorse any specific physicians, products or treatments even though they may be mentioned on this site.
