Clinical Study Evaluating the Effect of Losartan

August 4, 2024 updated by: Mona Abd El- Rafea Abdo, Tanta University

Clinical Study Evaluating the Effect of Losartan on Response Rate in Both Metastatic and Locally Advanced Pancreatic Cancer Patients

The pancreas is two organs packaged into one. The islets of Langerhans serve critical endocrine functions, and the exocrine portion is a major source of enzymes that are essential for digestion.

Pancreatic cancer (PC) is more commonly referred to as pancreatic infiltrating ductal adenocarcinoma in addition to being the second leading cause of cancer death in the United States, after lung cancer in 2020.

Whereas pancreatic cancer is the seventh cause of death from cancer in Asia in 2020. Although it is substantially less common than the other malignancies, pancreatic carcinoma is near the top of the list of killers because it is a highly aggressive carry.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Pancreatic cancer has multi step carcinogenesis, starting from Pancreatic Intra-ductal Neoplasia and ends with an invasive neoplastic lesion.Pancreatic cancer is most frequent in elder people; the risk of developing pancreatic cancer goes up as people age.

It is frequently found at an advanced stage, which contributes to five-year survival rates of 2-9%, ranking firmly the pancreatic cancer among all cancer sites in terms of prognostic outcomes for patients. In addition, it has a high trend to show nodal metastasis, hepatic, bone, or pulmonary metastasis.

Epidemiological data shows that pancreatic cancer is not very common but obvious it is one of the most neoplastic death-cause in the world.The Renin angiotensin system (RAS) is an important regulator of the cardiovascular system that was identified. in this system, angiotensinogen is converted to angiotensin (Ang) I and then to Ang II by renin and angiotensin-converting enzyme (ACE), respectively.

The Ang II activates the angiotensin type 1 receptor (AT1R). It has been suggested that RAS components are involved in the evolution of various cancers and tissues, like prostate, skin, and pancreatic cancer. In the pancreas, they are considered to mediate growth and lead to carcinogenesis.

High concentrations of Ang II have been reported together with up-regulated levels of AT1R in human with pancreatic cancer and malignant pancreatic tissues.

AT1R is known to activate phosphatidylinositol-specific-phosphodiesterase C enzyme after being activated by Ang II to produce phosphate inositol and 2-acylglycerol, which causes the entry of Ca2+ into cells, hence, activating protein kinase C and mitogen-activated protein kinase (MAPK).

MAPK has an important role in cell proliferation. Moreover, studies show that Ang II induces Vascular endothelial growth factor (VEGF) expression which is the main growth factor involved in angiogenesis.

Several studies have reported that RAS can increase the risk of metastasis in various cancers. Building upon these findings, RAS blockers may be expected to be beneficial in pancreatic cancer treatment.

Losartan is a RAS inhibitor currently well-known to decrease blood pressure. 10 It is demonstrated in several studies that Losartan can inhibit the effect of Ang II on cell proliferation and angiogenesis. In PC, it's suggested that Losartan increases drug delivery to the tumor, thus improving the chemotherapy effect.

Furthermore it increase the efficacy of Nano-therapeutics in pancreatic cancer of mice through enhancing both interstitial and trans-vascular transport. In another study it was found that Losartan raised DNA incorporation of Gemcitabine and enhanced its efficacy.

Studies

Over the past two decades have provided important information on the potential therapeutic use of RAS blocker drugs in cancer.Extensive preclinical data support the potential use of angiotensin II receptor blockers (ARBs) as anti-neoplastic agents in pancreatic cancer

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
      • Tanta, Egypt
        • Recruiting
        • Tanta University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and female pancreatic cancer patients aged ≥ 50 years old.
  • Hypertensive patient with BP ≥ 140/90 mm Hg.
  • Histologically confirmed metastatic pancreatic adenocarcinoma; or locally advanced pancreatic cancer patients.
  • All included patients must sign an informed consent

Exclusion Criteria:

  • Patients with serious concomitant systemic disorders as significant cardiac, renal, hepatic, or pulmonary morbidity.
  • Pregnant or lactating women and women of childbearing potential.
  • Patients received prior systemic fluoropyrimidine therapy within the past 10 years.
  • Prior un-anticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil, irinotecan, oxaliplatin, losartan, or any monoclonal antibody.
  • Patients with an active, known, or suspected autoimmune disease such as psoriasis.
  • Patients with a known positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus (HCV antibody) and patients with a known history of testing positive for (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Patients received a live vaccine or live attenuated vaccines as intranasal influenza vaccines within 30 days of the planned start of study therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group I (locally advanced PC patients):

Including three subset groups (A, B and C)

•Group I- A(control group): Fifteen hypertensive patients treated with antihypertensive agent except ARBS and ACEI with locally advanced PC on Folfirinox.

• Group I -B (are not treated with ARBs or ACEI prior PC diagnosis): Fifteen hypertensive patients with locally advanced PC and are not treated with ARBs or ACEI before PC diagnosis on the same chemotherapy treatment protocol as the control group in addition to losartan 50 mg once daily for one year after PC diagnosis.

• Group I-C (losartan was used for treatment of hypertension before and after PC diagnosis):Fifteen hypertensive patients with locally advanced PC and were treated with losartan one year before PC diagnosis on the same chemotherapy treatment protocol as the control group in addition to losartan 50 mg once daily for one year after PC diagnosis and the dose will be titrated up according to the patient's response.
Drug: Losartan 50mg Tab
The efficacy of losartan on response rate in both metastatic and locally advanced pancreatic cancer patients
Other Names:
  • Gemcitabine hydrochloride
Active Comparator: Group II (metastatic PC patients):

including three subset groups (A, B and C):

• Group II-A (control group): Fifteen hypertensive patients treated with antihypertensive agent except ARBS and ACEI with metastatic PC on Gemcitabine hydrochloride 1 gm. vial taken as 1000 mg/m2 IV over 30 min weekly for 7 weeks.

• Group II-B (are not treated with ARBs or ACEI prior diagnosis): Fifteen hypertensive patients with metastatic PC and are not treated with ARBs or ACEI before PC diagnosis on the same chemotherapy treatment protocol as the control group in addition to Losartan 50 mg once daily for one year after PC diagnosis.

• Group II-C (losartan was used for treatment of hypertension before and after PC diagnosis): Fifteen hypertensive patients with metastatic PC and were treated with losartan one year before PC diagnosis and on the same chemotherapy treatment protocol as the control group in addition to Losartan 50 mg once daily for one year after PC diagnosis
Drug: Losartan 50mg Tab
The efficacy of losartan on response rate in both metastatic and locally advanced pancreatic cancer patients
Other Names:
  • Gemcitabine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the patient response rate
Time Frame: one year
the patient response rate which will be measured using response evaluation criteria in solid tumors (RECIT 1.1).
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Investigators

  • Study Director: Osama Mohamed Hassan, Professor, Clinical Pharmacy Department Faculty of Pharmacy, Tanta University
  • Study Director: Sahar Mohamed El-Ghobashy, Professor, Clinical Pharmacy Department Faculty of Pharmacy, Tanta University
  • Study Chair: Mohamed Abdel Hamid Mohamed, Professor, Clinical Oncology Faculty of Medicine, Tanta University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2024

Primary Completion (Estimated)

August 10, 2026

Study Completion (Estimated)

August 20, 2026

Study Registration Dates

First Submitted

July 18, 2024

First Submitted That Met QC Criteria

August 4, 2024

First Posted (Actual)

August 6, 2024

Study Record Updates

Last Update Posted (Actual)

August 6, 2024

Last Update Submitted That Met QC Criteria

August 4, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mona Abd El-Rafea Mohamed

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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