Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

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

Objectives:

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

- Determine morbidity of this procedure in this patient population.

- Determine the impact of surgery and HIPEC on quality of life (QOL) and hormone excess.

- Examine patterns of recurrence (local versus systemic).

- Determine overall survival after optimal debulking and HIPEC in patients with IP spread of adrenocortical cancer.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Carcinomatosis; Adrenocortical Carcinoma
• Intervention / Treatment: Drug: Cisplatin; Drug: Sodium thiosulfate; Procedure: Cytoreductive surgery

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Kluger, MD; Phone Number: 212-305-6514; Email: mk2462@cumc.columbia.edu
• Study Contact Backup: Name: Vilma L Rosario; Phone Number: 212-305-6033; Email: vr2222@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032-3729
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Michael Kluger, MD
      • Contact: Michael Kluger, MD; Phone Number: 212-305-6514; Email: mk2462@cumc.columbia.edu
      • Sub-Investigator: Antonio T Fojo, MD
      • Contact: Vilma Rosario; Phone Number: 212-305-6033; Email: vr2222@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 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

• 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 aspartate aminotransferase (AST) and alanine aminotransferase (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.
  • Prothrombin time (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 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 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 (PFT) indicating an forced expiratory volume at one second (FEV1) less than 50% or a diffusing capacity of lung for carbon monoxide (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Surgery with HIPEC; Cytoreductive surgery followed by HIPEC with cisplatin and sodium thiosulfate

Drug: Cisplatin; Route of administration: Intraperitoneal for tumor treatment. Dose of 250 mg/m2 Drug 1 of the hyperthermic intraperitoneal chemotherapy (HIPEC); Other Names: Platinol; Drug: Sodium thiosulfate; Route of administration: Intravenous Loading dose of 7.5 gm/m2 over 20 minutes followed by 2.13 gm/m2/hr for 12 hours Drug 2 given intravenously during hyperthermic intraperitoneal chemotherapy (HIPEC); Other Names: Sodium thiosulfate injection; Procedure: Cytoreductive surgery; Standard of care: Surgical procedure used to remove tumors from patients with peritoneal tumors.; Other Names: Cytoreductive debulking surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The length of time after optimal debulking and heated intraperitoneal chemotherapy that a patient lives before there is clinical evidence of recurrent adrenocortical cancer.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity Rate	The frequency of post-operative complications.	Up to 5 years
Quality of Life (QOL) Score	This measures the impact of surgery and HIPEC on quality of life.	Up to 5 years
Overall Survival	The length of time people are alive after surgery and HIPEC for adrenocortical cancer.	Up to 5 years

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Michael Kluger, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 2, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cisplatin; Heated Cisplatin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Abdominal Neoplasms; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Carcinoma; Peritoneal Neoplasms; Adrenocortical Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Protective Agents; Anti-Bacterial Agents; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Sodium thiosulfate
• Other Study ID Numbers: AAAQ9194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No