Tadalafil Effect + Chemotherapy in Resectable Gastric/GEJ Cancer

NCT05709574 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00001728
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the ability of Tadalafil alone and in combination with neoadjuvant FLOT (5-Fluorouracil, Oxaliplatin, and Docetaxel) chemotherapy to suppress myeloid derived suppressor cells (MDSCs) in patients with resectable gastric or gastroesophageal junction adenocarcinoma. Resectable means the tumor may be removed through surgical intervention. Neoadjuvant chemotherapy is chemotherapy received before the primary course of treatment i.e.surgical intervention. The main questions it aims to answer are:

• Is Tadalafil treatment with FLOT feasible and safe?
• How does tadalafil treatment with FLOT affect the tumor microenvironment (TME)?
• Will 8 weeks of neoadjuvant exposure to tadalafil with chemotherapy reduce MDSCs in the TME? Participants will receive Tadalafil for 14 days followed by combination of Tadalafil + FLOT for approximately 8 weeks as a part of standard of care neoadjuvant treatment in the window between cancer diagnosis and surgical intervention to remove their tumor. Tumor tissue, blood, and urine will be collected at the start of the study, after 2 weeks of treatment with Tadalafil alone, and around the time of surgical intervention. Saliva will also be collected at the start of the study.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

PDE5,6i inhibitor; chemotherapeutic cell death; resectable Gastric/GEJ cancer; tadalafil; FLOT chemotherapy; Myeloid Derived Suppressor Cells (MDSCs)

Outcome Measures

Primary Outcomes (1)

• Evaluating the safety and tolerability of tadalafil treatment with FLOT chemotherapy by assessing the number of participants with treatment related adverse events usting CTCAE v. 5.0.

  To evaluate the safety and tolerability by assessing the number of participants with treatment related adverse events using CTCAE v5.0.

  10 weeks

Secondary Outcomes (2)

• Pathological response after PDE5 inhibition and treatment using Becker's Criteria

  10 weeks

• Radiographic response after PDE5 inhibition and treatment based on RECIST1.1

  10 weeks

Other Outcomes (14)

• Effect of Tadalafil on the myeloid derived suppressor cells (MDSCs) population as measured by 50% change in MDSCs

  8 weeks

• Change in tumor-intrinsic genetic biomarkers TLR9 SNP rs5743836 before and after treatment.

  10 weeks

• Change in intrinsic genetic biomarker MIR130b before and after treatment.

  10 weeks

Study Arms (1)

Tadalafil + chemotherapy

EXPERIMENTAL

Subjects will receive Tadalafil monotherapy for 2 weeks followed by Tadalafil in combination with neoadjuvant FLOT chemotherapy for 8 weeks in the window between their cancer diagnosis and surgical intervention.

Drug: Tadalafil 20 MG

Interventions

Tadalafil 20 MG DRUG

Tadalafil 20 mg tablets will be taken daily for 2 weeks alone and then for 8 weeks in combination with neoadjuvant chemotherapy in the window between gastric/GEJ adenocarcinoma diagnosis and interventional surgery.

Also known as: Cialis

Tadalafil + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage I-III (T1-3Nx) Gastric or GEJ (Siewert 3) adenocarcinoma, confirmed by histology or cytology.
• Radiographically measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Images (MRI or CT scan) must be completed within 28 days prior to treatment start.
• Age ≥ 18 years.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support within 2 weeks.
• White blood cell count ≥ 2500/µL including Lymphocyte count ≥ to 500/µL.
• Platelets ≥ 100,000/µL without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN. Patients with documented liver or bone metastases: ALP ≤ 5 x ULN.
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum albumin ≥ 2.8 g/dl.
• (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN.
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft- Gault equation:
• Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)
• Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85

You may not qualify if:

• Prior treatment for gastric cancer.
• Prior treatment with Tadalafil or other PDE inhibitors within 28 days.
• Known metastatic disease.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a) Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class II-IV, unstable angina pectoris, serious cardiac arrhythmias.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix III for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: i. Rash must cover \< 10% of body surface area. ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• iii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Active infection requiring systemic treatment with the following exceptions:
• Urinary tract infections.
• HCV on active treatment.
• Patients with SARS-COV-2 infections with the following exceptions:
• a) Recovery from active symptoms 30 days prior to treatment start.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

Arizona Cancer Center at UMC North/University Medical Center

Tucson, Arizona, 85719, United States

RECRUITING

MeSH Terms

Interventions

Tadalafil

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Junaid Arshad, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prisca Zimmerman

CONTACT

520-626-8286; priscaz@arizona.edu

Rachel E Jarrett

CONTACT

520-626-0375; rjarrett@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: February 2, 2023
• Study Start: April 20, 2023
• Primary Completion: March 30, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)