Surgery combined with heated chemotherapy for adrenocortical cancer

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

This study is testing if surgery followed by heated chemotherapy can help people with advanced adrenocortical cancer live longer and feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Columbia University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (New York, New York)
• Trial ID: NCT03127774 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of surgical debulking followed by heated intraperitoneal chemotherapy (HIPEC) using cisplatin in patients with adrenocortical carcinoma that has spread to the peritoneal cavity. The study will assess progression-free survival, overall survival, and the impact of the treatment on quality of life and hormone levels. Additionally, it will analyze the morbidity associated with the procedure and patterns of cancer recurrence. The approach leverages the synergy between hyperthermia and cisplatin to potentially improve outcomes for patients with minimal tumor volume.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed adrenocortical carcinoma that is primarily confined to the peritoneal cavity and is resectable.

Not a fit: Patients with extensive metastatic disease that is not amenable to surgical resection or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with advanced adrenocortical carcinoma.

How similar studies have performed: Previous studies using heated intraperitoneal chemotherapy with cisplatin in other cancers have shown promising results, suggesting potential for success in this novel application.

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

Where this trial is running

New York, New York

• Columbia University Medical Center — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Michael Kluger, MD — Columbia University
• Study coordinator: Michael Kluger, MD

Conditions: Adrenocortical Carcinoma, Peritoneal Carcinomatosis, Cisplatin, Heated Cisplatin