Phase II Trial of Surgical Resection and Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) for Adrenocortical Carcinoma

Inclusion Criteria

- 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 imaging

- All disease should be deemed resectable with negative margins (NED) 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

Including para-aortic lymph node metastases (stations 16 a1 and/or b2, see appendix D)

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

Note: lung lesions must be amenable to complete resection

Patients who present with both hepatic and peritoneal metastases must have no evidence of
extensive para-aortic/retro-pancreatic lymph node metastases

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. (See Appendix E)

- Greater than or equal to 18 years of age

- Able to understand and sign the Informed Consent Document

- Clinical performance status of ECOG 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/mm3 without the support of Filgrastim.

Platelet count greater than 75,000/mm3.

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 and ALT 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 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 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 or other chronic pulmonary restrictive disease with PFT's indicating an
FEV1 less than 50% or a DLCO 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 telangectasias.

- 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