Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare tumor with an overall 5-year mortality rate of 75 -
90% and an average survival from the time of diagnosis of 14.5 months. The treatment of
choice for a localized primary or recurrent tumor is surgical resection of all visible tumor
and involved organs. For unresectable metastatic or recurrent disease, mitotane,
aminoglutethimide, metapyrone, and ketoconazole are used. This would be the standard of care
alternative treatment.

Cisplatin is one of the most effective chemotherapeutic agents for ACC. Phase I and II trials
using heated intraperitoneal (IP) chemotherapy with cisplatin have been conducted in other
tumors that spread primarily to the peritoneal lining of the abdomen. Synergy has been
demonstrated for cisplatin and hyperthermia. The purpose of this trial is to determine if an
surgical approach with intraperitoneal administration of heated cisplatin when tumor volume
is minimal, can impact and improve on progression free survival.

INCLUSION CRITERIA

- Histologically proven ACC with the majority of disease confined to the peritoneal
cavity and resectable or amenable to radiofrequency ablation

- Disease evaluable by CT or PET (Positron Emission Tomography) imaging

- All disease should be deemed resectable based on imaging studies e.g.:

- Hepatic metastases (unilateral or bilateral less than or equal to 5 lesions, less
than or equal to 15 cm total diameter)

- Note: Hepatic lesions must be amenable to complete resection

- Primary peritoneal metastases (small disease load less than or equal to P2
disease) without massive ascites or intestinal obstruction

- Lung metastases (less than or equal to 3 unilateral/bilateral, 9 cm total
diameter)

- Note: lung lesions must be amenable to complete resection

- Note: Patients with both pulmonary and hepatic metastases will be enrolled at the
discretion of the PI

- Note: In situations where resection to Completeness of Cytoreduction Score (CC) 0
or 1 is uncertain, patients may undergo diagnostic laparoscopy prior to
enrollment to determine feasibility of resection.

- Greater than or equal to 18 years of age

- Able to understand and sign the Informed Consent Document

- Clinical performance status of ECOG (Eastern Cooperative Oncology Group) less than or
equal to 2

- Life expectancy of greater than three months

- Patients of both genders must be willing to practice birth control during and for four
months after receiving chemotherapy

- Hematology:

- Absolute neutrophil count greater than 1500/mm^3 without the support of
Filgrastim.

- Platelet count greater than 75,000/mm^3.

- Hemoglobin greater than 8.0 g/dl.

- Chemistry:

- Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine
clearance is greater than 60 mL/min/1.73 m2

- serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) within
5 times the upper limit of normal and a total serum bilirubin of less than 3
times the upper limit of normal, both of which define the upper limit of grade 2
treatment related toxicities.

- PT (prothrombin time) within 2 seconds of the upper limit of normal (INR less
than or equal to 1.8)

- Recovered from any toxicity to grade 2 or less from all prior chemotherapy,
immunotherapy or radiotherapy and be at least 30 days past the date of their last
treatment with the exception of mitotane which may be continued.

- Able to understand their disease and the exploratory nature of combining surgery and
HIPEC for this histology.

EXCLUSION CRITERIA

- Concomitant medical problems that would place the patient at unacceptable risk for a
major surgical procedure.

- History of congestive heart failure and/or an LVEF (left ventricular ejection
fraction) less than 40%

Note: Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g.,
greater than 65yo, diabetes, history of hypertension, elevated LDL, first degree relative
with coronary artery disease) will undergo full cardiac evaluation and will not be eligible
if they demonstrate significant irreversible ischemia on stress thallium or an ejection
fraction less than 40%.

- Significant COPD (chronic obstructive pulmonary disease) or other chronic pulmonary
restrictive disease with PFT (pulmonary function test) indicating an FEV1 (forced
expiratory volume at one second) less than 50% or a DLCO (diffusing capacity of lung for
carbon monoxide) less than 40% predicted for age.

Note: Patients who have shortness of breath with minimal exertion or who are at risk for
pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will
not be eligible if their FEV1 is less than 50% of expected.

- Grade 2 or greater neuropathy

- Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the chemotherapy on the fetus or infant.

- Brain metastases or a history of brain metastases

- Childs B or C cirrhosis

- Evidence of severe portal hypertension by history, endoscopy, or radiologic studies

Note: Any diagnosis of portal hypertension or clinical stigmata of such including but not
limited to gastric or esophageal varices, umbilical vein varices or telangiectasias.

- Weight less than 30 kg

- Active systemic infections, coagulation disorders or other major medical illnesses of
the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
arrhythmias, obstructive or restrictive pulmonary disease