Losartan and Hypofractionated Rx After Chemo for Tx of Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (SHAPER)

NCT04106856 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: HCI121104NCI-2019-05882P30CA042014
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of losartan and hypofractionated radiation therapy after chemotherapy in treating patients with pancreatic cancer that may or may not be removed by surgery (borderline resectable) or has spread from its original site of growth to nearby tissues or lymph nodes and is not amenable to surgical resection (locally advanced unresectable). Losartan may improve blood flow and allows for better tissue oxygenation. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving losartan and hypofractionated radiation therapy may work better in treating patients with pancreatic cancer compared to hypofractionated radiation therapy alone.

Conditions

Borderline Resectable Pancreatic Adenocarcinoma; Locally Advanced Pancreatic Ductal Adenocarcinoma; Locally Advanced Unresectable Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Grade 3 or higher gastrointestinal toxicity rate

  Will be graded according to Common Terminology Criteria for Adverse Events version (v) 5.0. The proportion of subjects that experience this endpoint will be tabulated along with an exact 90% binomial confidence interval (Clopper-Pearson).

  Up to 3 months (84 days) after completion of radiation therapy

Secondary Outcomes (5)

• Frequency of adverse events

  Up to 3 months (84 days) after completion of radiation therapy

• Response rate (clinical and/or pathologic partial response [PR] and complete response [CR])

  Up to 36 months post-treatment

• Progressive free survival (PFS)

  From the time of enrollment until disease progression or death (any cause), assessed up to 36 months post-treatment

• Overall survival (OS)

  From the patient?s first dose of study drug to death due to any cause, assessed up to 36 months post-treatment

• Number patients that require a medical intervention or hospitalization due to hypotension

  Up to 36 months post-treatment

Other Outcomes (1)

• Patient reported quality of life assessment- review of symptoms and how they interfere in life

  At study entry, during the final week of radiation therapy, and at each follow up visit

Study Arms (1)

Treatment (losartan, hypofractionated radiation therapy)

EXPERIMENTAL

Beginning on day 1, patients receive losartan potassium PO QD. Beginning day 14, patients also undergo hypofractionated radiation therapy over 15 fractions 5 days a week for up to 3 weeks. Patients continue to receive losartan potassium PO QD during radiation therapy and for 28 days after completion of radiation therapy. Patients may begin additional anti-cancer therapy per investigator discretion after the last dose of HRT. Losartan can be given concurrently with additional therapy and Losartan dosing can continue until 28 days after last dose of HRT, regardless of when additional therapy is started.

Radiation: Hypofractionated Radiation Therapy; Drug: Losartan; Drug: Losartan Potassium; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated Radiotherapy, hypofractionation

Treatment (losartan, hypofractionated radiation therapy)

Losartan DRUG

Given PO

Treatment (losartan, hypofractionated radiation therapy)

Losartan Potassium DRUG

Given PO

Also known as: Cozaar, losartan

Treatment (losartan, hypofractionated radiation therapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (losartan, hypofractionated radiation therapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (losartan, hypofractionated radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed pancreatic ductal adenocarcinoma
• Borderline resectable or locally advanced unresectable pancreas cancer as defined by the National Comprehensive Cancer Network (NCCN) and determined by a pancreatic surgeon prior to therapy. This can be confirmed by the surgeon?s documentation in the electronic medical record, by a treatment planning conference note, or by the signature of a pancreatic surgeon
• At least one infusion of FOLFIRINOX, NALIRIFOX, or gemcitabine based chemotherapy must have been attempted.
• No more than 6 months of chemotherapy as defined by standard cycle lengths (every other week infusions for FOLFIRINOX or NALIRIFOX, and 3 infusions per month for gemcitabine-based therapy). Each infusion of FOLFIRINOX or NALIRIFOX will be counted as 0.5 months. Three infusions of gemcitabine based chemotherapy will be counted as 1 month. If chemotherapy is given over a protracted period, then more than 6 months of chemotherapy may be acceptable. For example, if gemcitabine-based therapy is given every other week, then each infusion will still only count as 1/3 of a month toward the 6 month total. If a partial cycle of chemotherapy is given, that partial cycle will be counted proportional to the amount given. For example, if one of three planned infusions of gemcitabine based chemotherapy is given, it will be counted as 1/3 month.
• Enrollment must occur within 90 days of Day 1 of the last infusion given of chemotherapy. Patients who have primary tumor or regional lymph node progression on chemotherapy or prior to enrollment are eligible if no distant metastases are identified on the screening imaging assessment.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1500/uL
• Platelets \>= 100k/uL
• Total Bilirubin =\< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
• Serum creatinine \< 1.25 md/dL
• Serum potassium \< 5.0 mmol/L
• Negative serum or urine pregnancy test at screening for women of childbearing potential
• Highly effective contraception for both male and female subjects throughout the study and for at least 12 months after last study treatment administration if the risk of conception exists
• Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy

You may not qualify if:

• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen of this trial
• Distant metastases. Regional lymphatic disease is acceptable
• Prior radiation therapy or definitive resection for pancreatic cancer
• Uncontrolled gastric or duodenal ulcer disease within 28 days of registration
• Chronic cough, defined 30% of days over 3 months with active symptoms at enrollment or over 12 months with last active symptoms occurring 6 months prior to enrollment
• Symptomatic hypotension (blood pressure \< 90 systolic or \< 60 diastolic at screening vital sign assessment) that has the potential to interfere with the patient's safety or ability to complete protocol treatment, at the discretion of the treating investigator
• Patients taking \> 50mg losartan QD who, at the discretion of the treating investigator, cannot be reduced to the protocol defined regimen.
• Patients taking an angiotensin II receptor blocker or an angiotensin-converting enzyme inhibitor who, at the discretion of the treating investigator, cannot be safely discontinued prior to Day 1 dosing.
• Patients taking direct renin-angiotensin system inhibitors including aliskiren (Rasilez).
• Prior allergy to an angiotensin II receptor blocker
• Concurrent use of direct renin inhibitor including aliskiren (Rasilez)
• Patients with known history of:
• Heart failure. Patients with heart failure, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patients with a prior history of treatment with cardiotoxic agents should be evaluated for heart failure prior to enrollment at the discretion of the treating investigator.
• Solitary kidney, renal artery stenosis, or chronic renal failure

Sponsors & Collaborators

• University of Utah: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Radiation Dose Hypofractionation; Losartan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Shane Lloyd

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: September 27, 2019
• Study Start: August 8, 2019
• Primary Completion: December 6, 2024
• Study Completion (Estimated): August 8, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)