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.
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
Drug | Synonyms | Arms |
---|
Losartan | | Treatment (losartan, hypofractionated radiation therapy) |
Losartan Potassium | Cozaar, losartan | Treatment (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
Name | Type | Description | Interventions |
---|
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. | - 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
July 16, 2021