Brief Title
Surgery and Heated Chemotherapy for Adrenocortical Carcinoma
Official Title
Phase II Trial of Surgical Resection and Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) for Adrenocortical Carcinoma
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.)
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Intraperitoneal Progression Free Survival (PFS)
Secondary Outcome
Number of Patients With Treatment Related Morbidity Following the Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) Procedure
Condition
Adrenocortical Carcinoma
Intervention
Cisplatin
Study Arms / Comparison Groups
Cytoreductive surgery followed by HIPEC
Description: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
11
Start Date
April 12, 2013
Completion Date
August 9, 2018
Primary Completion Date
August 9, 2018
Eligibility Criteria
- INCLUSION CRITERIA
- 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
- 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
(international normalized ratio (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
Heated Intraperitoneal Peritoneal Chemotherapy (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 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
Gender
All
Ages
18 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Jeremy L Davis, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01833832
Organization ID
130114
Secondary IDs
13-C-0114
Responsible Party
Principal Investigator
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Jeremy L Davis, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
July 2019