Clinical Trials /

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

NCT04106856

Description:

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.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Losartan and Hypofractionated Rx After Chemo for Tx of Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (SHAPER)
  • Official Title: SHAPER: A Phase 1 Study of Losartan and Hypofractionated Radiation Therapy After Induction Chemotherapy for Borderline Resectable or Locally Advanced Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: HCI121104
  • SECONDARY ID: NCI-2019-05882
  • SECONDARY ID: HCI121104
  • SECONDARY ID: P30CA042014
  • NCT ID: NCT04106856

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

Interventions

DrugSynonymsArms
LosartanTreatment (losartan, hypofractionated radiation therapy)
Losartan PotassiumCozaar, losartanTreatment (losartan, hypofractionated radiation therapy)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. 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:

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

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

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

      EXPLORATORY OBJECTIVE:

      I. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (losartan, hypofractionated radiation therapy)ExperimentalBeginning 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.
  • Losartan
  • Losartan Potassium

Eligibility Criteria

        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

          -  Patient has received gemcitabine-based multi-agent chemotherapy regimen or
             fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) chemotherapy for
             1-6 months. Enrollment has to occur within 3 months of the day 1 of the last cycle
             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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Grade 3 or higher gastrointestinal toxicity rate
Time Frame:Up to 3 months (84 days) after completion of radiation therapy
Safety Issue:
Description: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

Measure:Frequency of adverse events
Time Frame:Up to 3 months (84 days) after completion of radiation therapy
Safety Issue:
Description:Will be graded according to Common Terminology Criteria for Adverse Events version (v) 5.0.
Measure:Response rate (clinical and/or pathologic partial response [PR] and complete response [CR])
Time Frame:Up to 36 months post-treatment
Safety Issue:
Description: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).
Measure:Progressive free survival (PFS)
Time Frame:From the time of enrollment until disease progression or death (any cause), assessed up to 36 months post-treatment
Safety Issue:
Description:Kaplan-Meier methods will be used to report PFS.
Measure:Overall survival (OS)
Time Frame:From the patient?s first dose of study drug to death due to any cause, assessed up to 36 months post-treatment
Safety Issue:
Description:Kaplan-Meier methods will be used to report OS.
Measure:Number patients that require a medical intervention or hospitalization due to hypotension
Time Frame:Up to 36 months post-treatment
Safety Issue:
Description:Will be analyzed descriptively.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Last Updated

April 8, 2020