Tadalafil Effect + Chemotherapy in Resectable Gastric/GEJ Cancer

Inclusion Criteria: 1. Stage I-III (T1-3Nx) Gastric or GEJ (Siewert 3) adenocarcinoma, confirmed by histology or cytology. 2. 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. 3. Age ≥ 18 years. 4. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support within 2 weeks. 2. White blood cell count ≥ 2500/µL including Lymphocyte count ≥ to 500/µL. 3. Platelets ≥ 100,000/µL without transfusion. 4. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 5. 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. 6. Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN). 7. Serum albumin ≥ 2.8 g/dl. 8. (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN. 9. 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 5. ECOG performance status ≤ 1. 6. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment. 7. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site. 8. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: 1. Prior treatment for gastric cancer. 2. Prior treatment with Tadalafil or other PDE inhibitors within 28 days. 3. Known metastatic disease. 4. 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. ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment. iv. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment. v. Ventricular tachyarrhythmia requiring ongoing treatment vi. Unstable angina pectoris vii. Sinus bradycardia b) Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. iii. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment. 5. 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: 1. Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. 2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. 3. 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. 6. Active infection requiring systemic treatment with the following exceptions: 1. Urinary tract infections. 2. HCV on active treatment. 7. Patients with SARS-COV-2 infections with the following exceptions: a) Recovery from active symptoms 30 days prior to treatment start. 8. Known history of infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or a known positive test for tuberculosis due to tuberculosis infection. 9. Concomitant medication uses of nitrates, α-blockers and other interacting medications (CYP3A4 inhibitors and CYP3A4 inductors). 10. Other clinically significant disorders as deemed by the investigator, that would preclude safe study participation. 1. Serious non-healing wound/ulcer/bone fracture. 2. Uncompensated/symptomatic hypothyroidism. 3. Moderate to severe hepatic impairment. 11. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 12. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: 1. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. 2. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. 13. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment of within 6 months after the final dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within screening. Test will need to be repeated if last completed \>3 days prior to initiation of study treatment. 14. Inability to swallow tablets. 15. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 16. Previous episode of Non-arteritic anterior ischemic optic neuropathy (NAION) 17. Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.