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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Adrenocortical Carcinoma

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Trial Information

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

The investigators hypothesize that IL-13-PE will cause cancer regression in patients with
metastatic and locally advanced adrenocortical carcinoma (ACC) and other malignancies with
high IL13Rα2 expression level given the following:

- High levels of interleukin-13 receptor alpha 2 (IL13Rα2) are observed in ACC and in
malignant pheochromocytoma, pancreatic ductal adenocarcinoma, and hepatocellular

- IL13Rα2 regulates cellular proliferation and invasion of ACC cells.

- IL-13-PE is highly effective in causing cell death in IL13Rα2 positive ACC cells, and
causes tumor regression and prolonged survival in an ACC xenograft nude mice model.

The purposes of this study are:

- To determine the safety and maximal tolerated dose of IL-13-PE in patients with
metastatic and locally advanced ACC and other malignancies with high IL13Rα2 expression

- To determine response rate and progression-free survival in patients with recurrent,
metastatic, or primary unresectable ACC treated with IL-13-PE.

- Evaluate response to IL-13-PE with functional imaging as compared to axial imaging.

- Determine if response to IL-13-PE treatment is associated with IL13Rα2 expression

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose in Phase 1 of the study

Outcome Time Frame:

Phase 1 of the study (up to 5 days)

Safety Issue:


Principal Investigator

Electron Kebebew, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institutes of Health (NIH)


United States: Food and Drug Administration

Study ID:




Start Date:

December 2012

Completion Date:

December 2016

Related Keywords:

  • Adrenocortical Carcinoma
  • ACC
  • Carcinoma
  • Adrenocortical Carcinoma



NCI/NIH Bethesda, Maryland  20892