Surgery and Heated Chemotherapy for Adrenocortical Carcinoma

Phase 2

Completed

Conditions: Peritoneal Carcinomatosis
Adrenocortical Carcinoma

Interventions: Drug: Cisplatin
Procedure: Cytoreductive surgery
Drug: sodium thiosulfate

Registration Number: NCT01833832

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- Adrenocortical carcinoma (ACC) is a rare tumor of the adrenal gland. Few people who develop this disease live more than 5 years after being diagnosed. Those whose tumors have spread inside their abdomen may have an especially poor outcome. In these cases, traditional chemotherapy is not very effective. One possible new treatment is aggressive surgery with heated chemotherapy. This type of treatment has been more effective for other types of cancer in the abdomen. Researchers want to see this if approach can improve the outcomes of people with ACC.

Objectives:

- To test the safety and effectiveness of surgery and heated chemotherapy for ACC.

Eligibility:

- Individuals at least 18 years of age who have advanced ACC.

Design:

* Participants will be screened with a physical exam and medical history. Blood samples will be collected. Heart function tests will be given. Imaging studies will be used to locate the surgical sites before the operation.

* Participants will have surgery to remove ACC tumor tissue. After the tumors have been removed, they will have heated chemotherapy with cisplatin. The heat may help weaken any remaining cancer cells and make them easier to destroy. It will also focus the treatment on the tumor sites, rather than the whole body.

* Participants will recover in the hospital for several days after surgery. They will have regular follow-up visits to monitor the outcome of the surgery.

Detailed Description: Background:

* Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5 to 2 per million people per year and has a very poor prognosis 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. For unresectable metastatic or recurrent disease, mitotane, aminoglutethimide, metapyrone, and ketoconazole are used.

* Cisplatin is one of the most effective chemotherapeutic agents for ACC. In the Surgery Branch we have conducted Phase I and II trials using heated intraperitoneal (IP) chemotherapy with cisplatin for primary peritoneal mesothelioma, low grade appendiceal adenocarcinoma, ovarian malignancies, and high grade adenocarcinoma of the gastrointestinal tract. Synergy has been demonstrated for cisplatin and hyperthermia.

* The purpose of this trial is to determine if an aggressive surgical approach with intraperitoneal administration of heated cisplatin when tumor volume is minimal, can impact and improve on progression free survival.

Objectives:

- To determine IP progression free survival after optimal debulking and heated IP chemotherapy with cisplatin in patients with IP spread of adrenocortical cancer

Eligibility:

- Histologically proven ACC evaluable by computed tomography (CT) imaging with the majority of disease confined to the peritoneal cavity and surgically resectable to a residual size of less than 1 cm or amenable to radiofrequency ablation in patients who are \> 18 years of age.

Design:

- This is a classic phase 2 trial to determine efficacy of this therapeutic strategy in ACC. Patients will undergo cytoreductive surgery to achieve a CCR of 0 or 1.

Patients who are successfully debulked will then undergo hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin.

Patients will be evaluated by associate investigators in coordination with the Principal Investigator for eligibility. Due to its exploratory nature, up to 30 patients may be enrolled to obtain 24 evaluable patients. (Patients must undergo successful debulking and HIPEC to be considered evaluable.)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cytoreductive surgery followed by HIPEC	Cytoreductive surgery	Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin
Cytoreductive surgery followed by HIPEC	sodium thiosulfate	Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin
Cytoreductive surgery followed by HIPEC	Cisplatin	Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin

Primary Outcome Measures

Name	Time	Method
Intraperitoneal Progression Free Survival (PFS)	Amount of time subject survives without intraperitoneal disease progression after treatment, an average of 17 months	Amount of time subject survives without intraperitoneal disease progression after treatment. Disease progression is defined as imageable tumor nodules or increasing ascites persistent on computed tomography (CT) scan as interpreted by the official interpretation of the imaging studies.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Treatment Related Morbidity Following the Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) Procedure	Patients were assessed every 3 months up to an average of 17 months.	Patients who died following the HIPEC procedure. The HIPEC is a surgical procedure in which two large bore catheters are inserted in the abdominal wall over the liver and pelvis. The physician closes the abdominal fascia and the catheters are connected to a perfusion circuit. The temperature of the catheters is carefully monitored while the physician ensures the perfusion is distributed properly by manually moving the abdomen.
The Functional Assessment of Cancer Therapy-Colorectal Quality of Life (FACT-G) (QOL) Score Prior to Surgery, 6 Weeks After Surgery, and 3 Months After Surgery	Prior to surgery, 6 weeks post surgery, and 3 months post surgery	QOL characteristics were collected using The Functional Assessment of Cancer Therapy-Colorectal Quality of Life (QOL) questionnaire version 4, a validated survey that interrogates physical, emotional, functional, and social well being in cancer related issues on a 5-point scale. Scores range from 0 to 108 points. Higher scores are consistent with a better outcome.
Percentage of Participants Who Survived 5-years Post Treatment	5 years	Percentage of participants who are alive after treatment.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	Date treatment consent signed to date off study, approximately 34 months and 28 days.	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.