Surgery and Heated Chemotherapy for Adrenocortical Carcinoma

NCT01833832 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13011413-C-0114
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Adrenocortical Carcinoma; Peritoneal Carcinomatosis

Keywords

Synergy for Cisplatin and Hyperthermia; Rare Tumor; Poor Prognosis

Outcome Measures

Primary Outcomes (1)

• Intraperitoneal Progression Free Survival (PFS)

  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.

  Amount of time subject survives without intraperitoneal disease progression after treatment, an average of 17 months

Secondary Outcomes (4)

• 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.

• Percentage of Participants Who Survived 5-years Post Treatment

  5 years

• 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

• 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.

Study Arms (1)

Cytoreductive surgery followed by HIPEC

EXPERIMENTAL

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin

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

Interventions

Cisplatin DRUG

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

Also known as: Platinol

Cytoreductive surgery followed by HIPEC

Cytoreductive surgery PROCEDURE

Patients will undergo cytoreductive surgery to achieve a Completeness of Cytoreduction Score (CC) of 0 or 1.

Cytoreductive surgery followed by HIPEC

sodium thiosulfate DRUG

sodium thiosulfate will be given to limit the toxicity of cisplatin

Cytoreductive surgery followed by HIPEC

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven Adrenocortical carcinoma (ACC) with the majority of disease confined to the peritoneal cavity and resectable or amenable to radiofrequency ablation
• Disease evaluable by computed tomography (CT) or positron emission tomography (PET) 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 principal investigator (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 Eastern Cooperative Oncology Group (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

You may not qualify if:

• Concomitant medical problems that would place the patient at unacceptable risk for a major surgical procedure.
• History of congestive heart failure and/or an left ventricular ejection fraction (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 low-density lipoproteins (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 Chronic Obstructive Pulmonary Disease (COPD) or other chronic pulmonary restrictive disease with pulmonary function test (PFTs) indicating an forced expiratory volume 1 (FEV1) less than 50% or a Carbon monoxide diffusing capacity (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 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Datrice NM, Langan RC, Ripley RT, Kemp CD, Steinberg SM, Wood BJ, Libutti SK, Fojo T, Schrump DS, Avital I. Operative management for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol. 2012 Jun 1;105(7):709-13. doi: 10.1002/jso.23015. Epub 2011 Dec 20.

  PMID: 22189845 BACKGROUND

• Leboulleux S, Deandreis D, Al Ghuzlan A, Auperin A, Goere D, Dromain C, Elias D, Caillou B, Travagli JP, De Baere T, Lumbroso J, Young J, Schlumberger M, Baudin E. Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? Eur J Endocrinol. 2010 Jun;162(6):1147-53. doi: 10.1530/EJE-09-1096. Epub 2010 Mar 26.

  PMID: 20348273 BACKGROUND

• Feldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, Steinberg SM, Liewehr DJ, Kleiner DE, Alexander HR. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol. 2003 Dec 15;21(24):4560-7. doi: 10.1200/JCO.2003.04.150.

  PMID: 14673042 BACKGROUND

• Hughes MS, Lo WM, Beresnev T, Merino M, Shutack Y, Ripley RT, Hernandez JM, Davis JL. A Phase II Trial of Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Adrenocortical Carcinoma. J Surg Res. 2018 Dec;232:383-388. doi: 10.1016/j.jss.2018.06.012.

  PMID: 30463745 RESULT

MeSH Terms

Conditions

Adrenocortical Carcinoma; Peritoneal Neoplasms; Hyperthermia

Interventions

Cisplatin; Cytoreduction Surgical Procedures; sodium thiosulfate

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Jeremy Davis
• Organization: National Cancer Institute

jeremy.davis@nih.gov

240-760-6229

Study Officials

• Jeremy L Davis, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: April 12, 2013
• Primary Completion: August 9, 2018
• Study Completion: August 9, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 30, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)