A Phase 1 Trial of AVN944, an IMPDH Inhibitor, in Adults With Advanced Stage Solid Tumors

-INCLUSION CRITERIA:

1. Patients must have histologically confirmed malignancy (histopathological documentation of cancer confirmed in the NCI Laboratory of Pathology at the National Institutes of Health, the Pathology Department at Walter Reed Medical Center, or the Pathology Department at National Naval Medical Center, prior to starting this study) that is metastatic or unresectable and for which standard therapies do not exist or are no longer effective.

2. Patients must be at least 4 weeks since prior chemotherapy or radiation therapy and 2 weeks since prior hormonal therapy except for gonadotropin releasing hormone (GnRH) analogues and any acute or serious side effects of those therapies should be Grade less than 1 or returned to baseline

3. Patients must be able and willing to take oral capsules.

4. ECOG performance status less than or equal to 2

5. Life expectancy of greater than 3 months

6. Patients must have acceptable organ and marrow function as defined below:

   • Leukocytes greater than or equal to 3,000/mcL
   • Absolute Neutrophil Count greater than or equal to 1,500/mcL
   • Platelets greater than or equal to 100,000/mcL
   • Total Bilirubin less than or equal to 1.5 times institutional ULN (patients with known Gilberts syndrome may have values as high as less than or equal to 3.0 X ULN)
   • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
   • Creatinine less than or equal to 1.5 times institutional upper limit of normal

7. The effects of AVN944 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

8. Ability to understand and the willingness to sign a written informed consent document.

9. Age greater than or equal to 18 Years. Because no dosing or adverse event data are currently available on the use of AVN944 in patients less than 18 years of age, children are excluded from this study.

EXCLUSION CRITERIA:

1. Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 14 days of the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication). Clinically significant toxicities from this therapy must have resolved to less than Grade 2.

2. Patients with known active brain metastases or other CNS involvement with less than 6 months since curative-intent treatment

3. Patients receiving growth factors

4. Prior treatment with an IMPDH-inhibitor e.g. Mycophenolate Mofetil, & Tiazofurin

5. Uncontrolled current illness requiring hospitalization or intravenous antibiotics within the past 7 days

6. Pregnant women are excluded from this study because AVN944 agent has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AVN944, breastfeeding should be discontinued if the mother is treated with AVN944.

7. History of solid organ transplant and are on IMPDH inhibitors (mycophenolate mofetil) therapy

8. HIV-positive patients

9. The following medications and/or treatments are not permitted during the trial (i.e., through completion of the post treatment follow-up) and would constitute exclusion from the protocol:

   • Any other investigational treatment
   • Any cytotoxic chemotherapy
   • Any other systemic anti-neoplastic therapy including, but not limited to, immunotherapy or monoclonal antibody therapy.
   • Any radiotherapy, including systemically administered radioisotopes.
   • Systemic corticosteroids.
   • Any hormonal therapy except GnRH agonists / antagonists for patients with prostate cancer or medroxyprogesterone
   • Growth factors

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety