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Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

Primary Purpose

Adrenocortical Carcinoma, Peritoneal Carcinomatosis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Sodium thiosulfate
Cytoreductive surgery
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenocortical Carcinoma focused on measuring Cisplatin, Heated Cisplatin

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Columbia University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Surgery with HIPEC

Arm Description

Cytoreductive surgery followed by HIPEC with cisplatin and sodium thiosulfate

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
April 2, 2017
Last Updated
September 11, 2023
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT03127774
Brief Title
Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma
Official Title
Phase II Trial of Surgical Resection and Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) for Adrenocortical Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 22, 2017 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenocortical Carcinoma, Peritoneal Carcinomatosis
Keywords
Cisplatin, Heated Cisplatin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Patients who are successfully debulked will undergo heated intraperitoneal chemotherapy with cisplatin.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Surgery with HIPEC
Arm Type
Experimental
Arm Description
Cytoreductive surgery followed by HIPEC with cisplatin and sodium thiosulfate
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol
Intervention Description
Route of administration: Intraperitoneal for tumor treatment. Dose of 250 mg/m2 Drug 1 of the hyperthermic intraperitoneal chemotherapy (HIPEC)
Intervention Type
Drug
Intervention Name(s)
Sodium thiosulfate
Other Intervention Name(s)
Sodium thiosulfate injection
Intervention Description
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)
Intervention Type
Procedure
Intervention Name(s)
Cytoreductive surgery
Other Intervention Name(s)
Cytoreductive debulking surgery
Intervention Description
Standard of care: Surgical procedure used to remove tumors from patients with peritoneal tumors.
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
The length of time after optimal debulking and heated intraperitoneal chemotherapy that a patient lives before there is clinical evidence of recurrent adrenocortical cancer.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Morbidity Rate
Description
The frequency of post-operative complications.
Time Frame
Up to 5 years
Title
Quality of Life (QOL) Score
Description
This measures the impact of surgery and HIPEC on quality of life.
Time Frame
Up to 5 years
Title
Overall Survival
Description
The length of time people are alive after surgery and HIPEC for adrenocortical cancer.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Kluger, MD
Phone
212-305-6514
Email
mk2462@cumc.columbia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Vilma L Rosario
Phone
212-305-6033
Email
vr2222@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Kluger, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032-3729
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Kluger, MD
Phone
212-305-6514
Email
mk2462@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Vilma Rosario
Phone
212-305-6033
Email
vr2222@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Michael Kluger, MD
First Name & Middle Initial & Last Name & Degree
Antonio T Fojo, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma

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