GEM+Nab-Paclitaxel Plus Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer

NCT05861336 | Withdrawn Phase 2

• 1 other identifier: IRST157.04
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• margin-negative resection rate (R0)

  80 months

• progression-free survival (PFS)

  80 months

• overall survival (OS)

  80 months

• biomarker blood response

  80 months

• Incidence of Treatment-Emergent Adverse Events [Toxicity]

  80 months

Study Arms (1)

Chemotherapy+Losartan+Stereotactic Radiation

EXPERIMENTAL

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 day during induction chemotherapy and maintained until starting SBRT. SBRT will be administered in 7 consecutive fractions for a total dose of 35-42 Gy if no progression will be observed after induction therapy.

Drug: Losartan; Drug: Gemcitabine; Drug: Nab paclitaxel; Radiation: Stereotactic Body Radiation Therapy

Interventions

Losartan DRUG

Losartan will be administered at the dose of 25 mg PO qd starting on Cycle 1 Day 1. If this dose will be tolerated during week 1, escalation to 50 mg PO qd at Cycle 1 Day 8

Chemotherapy+Losartan+Stereotactic Radiation

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 days

Chemotherapy+Losartan+Stereotactic Radiation

Nab paclitaxel DRUG

nab-paclitaxel 125 mg/m2 on days 1, 8, and 15

Chemotherapy+Losartan+Stereotactic Radiation

Stereotactic Body Radiation Therapy RADIATION

7 consecutive fractions for a total dose of 35-42 Gy

Chemotherapy+Losartan+Stereotactic Radiation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed pancreatic carcinoma
• Clinical stage I-III, according to tumor, nodes and metastases (TNM) 8th ed.
• Locally advanced disease, as defined per National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 (Appendix D)
• Baseline systolic blood pressure (SBP) ≥ 100 mmHg (baseline SBP will be documented during the enrolment visit in a resting, seated position at least five minutes apart; SBP will be established as the average of the two readings; if SBP is borderline it may be measured in the other arm);
• Age \>18 years and ≤75 years.
• Life expectancy greater than 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Presence of at least one measurable lesion in agreement to RECIST 1.1 criteria
• Patients must have normal organ and marrow function as defined below:
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence, prior to study entry and continuing throughout the study period and for 6 months after final study drug administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Clinical stage IV, according to TNM 8th ed.
• Patients who have previously received chemotherapy or radiotherapy for pancreatic cancer.
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agent used in the study.
• Serious concomitant systemic disorders incompatible with the study (at discretion of the investigator);
• Patient already treated on other Losartan dosages than those prescribed by protocol or treated on other Angiotensin II Receptor Blockers (ARB) therapy for hypertension or renal protection (with diabetes) at the time of enrolment;
• Baseline hypotension, defined as systolic BP lower than 100 mmHg on two readings obtained on two separated days prior to study enrolment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (2)

U.O. Radioterapia IRCCS IRST

Meldola, Forlì, 47014, Italy

Location

UO Oncologia, AUSL della Romagna

Ravenna, 48121, Italy

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Losartan; Gemcitabine; Taxes; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Economics; Health Care Economics and Organizations; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Antonino Romeo, MD

  IRCCS IRST

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: May 16, 2023
• Study Start: June 14, 2023
• Primary Completion: December 23, 2024
• Study Completion: December 23, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)