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

Sponsor
University of Utah (Other)
Overall Status
Recruiting
CT.gov ID
NCT04106856
Collaborator
National Cancer Institute (NCI) (NIH)
20
1
1
72
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Radiation: Hypofractionated Radiation Therapy
  • Drug: Losartan
  • Drug: Losartan Potassium
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
Phase 1

Detailed Description

PRIMARY OBJECTIVE:
  1. To assess the safety of losartan potassium (losartan) in combination with hypofractionated radiation treatment for patients with stable or locally progressive pancreatic ductal adenocarcinoma (PDAC) after induction chemotherapy.
SECONDARY OBJECTIVES:
  1. To assess the safety of losartan in combination with HRT for patients with stable or locally progressive PDAC after induction chemotherapy.

  2. To assess the efficacy of losartan in combination with HRT for patients with stable or locally progressive PDAC after induction chemotherapy.

  3. To assess the rate of hypotensive adverse events grade >= 3.

EXPLORATORY OBJECTIVE:
  1. To assess patient reported quality of life.
OUTLINE:

Beginning day 1, patients receive losartan potassium orally (PO) once daily (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.

After completion of study treatment, patients are followed up at 28 and 84 days, every 3 months for 12 months, and then every 6 months for up to 36 months.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
SHAPER: A Phase 1 Study of Losartan and Hypofractionated Radiation Therapy After Induction Chemotherapy for Borderline Resectable or Locally Advanced Pancreatic Cancer
Actual Study Start Date :
Aug 8, 2019
Anticipated Primary Completion Date :
Aug 8, 2024
Anticipated Study Completion Date :
Aug 8, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (losartan, hypofractionated radiation therapy)

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
Undergo hypofractionated radiation therapy
Other Names:
  • Hypofractionated Radiotherapy
  • hypofractionation
  • Drug: Losartan
    Given PO

    Drug: Losartan Potassium
    Given PO
    Other Names:
  • Cozaar
  • losartan
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. Grade 3 or higher gastrointestinal toxicity rate [Up to 3 months (84 days) after completion of radiation therapy]

      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).

    Secondary Outcome Measures

    1. Frequency of adverse events [Up to 3 months (84 days) after completion of radiation therapy]

      Will be graded according to Common Terminology Criteria for Adverse Events version (v) 5.0.

    2. Response rate (clinical and/or pathologic partial response [PR] and complete response [CR]) [Up to 36 months post-treatment]

      Will be described using Response Evaluation Criteria in Solid Tumors v1.1. The proportion of subjects with a PR and CR will be reported along with exact binomial confidence intervals (Clopper-Pearson).

    3. Progressive free survival (PFS) [From the time of enrollment until disease progression or death (any cause), assessed up to 36 months post-treatment]

      Kaplan-Meier methods will be used to report PFS.

    4. 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]

      Kaplan-Meier methods will be used to report OS.

    5. Number patients that require a medical intervention or hospitalization due to hypotension [Up to 36 months post-treatment]

      Will be analyzed descriptively.

    Other Outcome Measures

    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]

      Will be assessed using MD Anderson Symptom Inventory-Gastrointestinal (MDASI-GI).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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 or gemcitabine based chemotherapy must have been attempted.

    • No more than 6 months of chemotherapy. Each completed cycle of FOLFIRINOX will be counted as 0.5 months. Each completed cycle of gemcitabine based chemotherapy will be counted as 1 month. If a partial cycle of chemotherapy is given, that partial cycle will be counted proportional to the amount given. E.G. 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.

    • Measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

    • 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

    • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

    Exclusion Criteria:
    • 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

    • Human immunodeficiency virus (HIV)-infected patients who are not on effective anti-retroviral therapy or have a detectable viral load within 6 months of trial entry

    • Patients with known evidence of chronic hepatitis B virus (HBV) infection and a detectable HBV viral load

    • Patients with a history of hepatitis C virus (HCV) infection who have not been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

    • Subject is currently enrolled on another investigational treatment study for pancreas cancer

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • University of Utah
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Shane Lloyd, Huntsman Cancer Institute/ University of Utah

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Utah
    ClinicalTrials.gov Identifier:
    NCT04106856
    Other Study ID Numbers:
    • HCI121104
    • NCI-2019-05882
    • HCI121104
    • P30CA042014
    First Posted:
    Sep 27, 2019
    Last Update Posted:
    May 5, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 5, 2022