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

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ClinicalTrials.gov Identifier: NCT04106856
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Utah

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
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 Radiation: Hypofractionated Radiation Therapy Drug: Losartan Drug: Losartan Potassium Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 8, 2019
Estimated Primary Completion Date : August 8, 2024
Estimated Study Completion Date : August 8, 2025

Resource links provided by the National Library of Medicine


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.
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 Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Grade 3 or higher gastrointestinal toxicity rate [ Time Frame: 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 [ Time Frame: 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]) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04106856


Contacts
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Contact: Mitchell Shea 801-587-4756 mitch.shea@hci.utah.edu

Locations
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United States, Utah
Huntsman Cancer Institute/University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Shane Lloyd    801-585-0255    shane.lloyd@hci.utah.edu   
Principal Investigator: Shane Lloyd         
Sponsors and Collaborators
University of Utah
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Shane Lloyd Huntsman Cancer Institute/ University of Utah
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Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT04106856    
Other Study ID Numbers: HCI121104
NCI-2019-05882 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HCI121104 ( Other Identifier: Huntsman Cancer Institute/University of Utah )
P30CA042014 ( U.S. NIH Grant/Contract )
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action