Study of Sildenafil as a Therapy for Fatigue in Pancreatic Cancer

Phase I Assessment of NO Mediated Signaling in Cancer Cachexia

Investigation of the effects of daily sildenafil on patients with pancreatic or cholangiocarcinoma cancer undergoing treatment.

This is a double-blinded, placebo-controlled trial in men and women, 40-75 years old, diagnosed with pancreatic or cholangiocarcinoma cancer. Patients will receive placebo or sildenafil daily for 4 weeks during their initial chemotherapy cycle.

Inclusion Criteria:

1. Men and women, aged 40-75 years.

2. Diagnosed with Stage III or IV pancreatic or cholangiocarcinoma receiving the following therapy:

   • Neoadjuvant chemotherapy
   • Surgical resection followed by chemotherapy.

3. Able to comprehend risks and sign a consent form.

4. Performance Status of 0-2.

Exclusion Criteria:

1. Significant renal or heart disease or any acute metabolic disease.
2. Evidence of hepatitis as indicated by a 3-fold increase in of 2 out of 3 liver enzymes.
3. Diabetes mellitus or other untreated endocrine disease.
4. Recent (within 3 months) treatment with anabolic steroids.
5. Ongoing anticoagulant therapy.
6. Androgen secreting tumors of the ovary and adrenal or any ovarian tumor (e.g., Sertoli-Leydig).
7. Polycystic ovary syndrome (PCOS) and/or hyperthecosis.
8. Non-classical adrenal hyperplasia.
9. Cushing's syndrome.
10. Glucocorticoid resistance.
11. Pregnancy.
12. Hyperprolactinoma, hypothyroidism.
13. Use of nitrates.
14. Use of alpha blockers.
15. Use of protease inhibitors.
16. Use of cytochrome p450 inhibitors.
17. Systolic blood pressure <100 or >150, diastolic blood pressure <60 or >90. This range is smaller than the acceptable range stated in the prescribing information for sildenafil (>90/50 and <170/110).
18. Peripheral vascular disease.
19. Use of a phosphodiesterase 5 inhibitor.
20. Any other circumstance deemed exclusionary by the PI or study physician.