A Phase I/II Trial of IL-13-PE in Patients With Treatment Refractory Malignancies With a Focus on Metastatic and Locally Advanced Adrenocortical Carcinoma

Inclusion Criteria:

1. Age ≥18.

2. Pathological confirmation of adrenocortical carcinoma (ACC) or malignant
pheochromocytoma, pancreatic adenocarcinoma, and hepatocellular carcinoma. Tumor
positive for IL13Rα2 by immunohistochemistry (≥ 30% of the tumor). Confirmation of
tumor positivity will be done at the Laboratory of Pathology, NCI.

3. Subjects with hepatocellular carcinoma must have a Child-Pugh classification of "A".

4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
at presentation.

5. Patients must have failed standard treatment:

- Surgical resection, if possible, for ACC and malignant pheochromocytoma.

- Surgical resection, if possible, for pancreatic adenocarcinoma and
hepatocellular carcinoma.

- Failed at least one FDA approved systemic chemotherapy regimen for pancreatic
adenocarcinoma (eg, fluorouracil, erlotinib, gemcitabine, and/or mitomycin) and
hepatocellular carcinoma (eg, sorafenib).

6. Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to
starting treatment with this protocol.

7. Prior or current mitotane therapy is allowed if patients are on the therapy to
control hypercortisolemia and have not had a response to the therapy and are
tolerating their dose.

8. No concurrent other investigational therapy.

9. No currently-active central nervous system (CNS) metastasis; patients may have a
history of treated brain metastases.

10. Life expectancy more than 12 weeks.

11. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

12. Good organ function, including:

- Hgb ≥ 8.0 gm/dL; ANC ≥ 1,000/mm^3; platelets ≥ 75,000/mm^3.

- AST and ALT ≤ 3 x Upper Limit Normal.

- Bilirubin ≤ Upper Limit Normal.

- Creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels
above institutional normal.

13. No infection requiring parenteral antibiotics.

14. Sero-negative for HIV antibody.

15. Sero-negative for Hepatitis B and Hepatitis C.

16. Not pregnant or nursing. Sexually-active patients must agree to use an effective
method of contraception prior to and for 4 months following treatment.

17. Able to give informed consent.

Exclusion Criteria:

1. Current coexisting malignancy other than basal cell carcinoma.

2. Women of child-bearing potential who are pregnant or breastfeeding. Additionally,
patients who become pregnant while on study protocol will be discontinued
immediately.

3. Active systemic infections, coagulation disorders, or other major medical illnesses.

4. Proteinuria ≥ 2+; urinary protein ≥ 1.0 g/24 hours.