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Adrenocortical CarcinomaPhase 2NCT01833832

Surgery and Heated Chemotherapy for Adrenocortical Carcinoma

A Phase 2 study testing Cisplatin, Cytoreductive surgery and sodium thiosulfate in people with Adrenocortical Carcinoma and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Cisplatin, Cytoreductive surgery and sodium thiosulfate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
12 Apr 2013to 9 Aug 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 25Show fewer
  • 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.

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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.
Read more

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.
Read the 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.)

Being tested
Cisplatin, Cytoreductive surgery, sodium thiosulfate
Keywords
Synergy for Cisplatin and Hyperthermia, Rare Tumor, Poor Prognosis
Medical subject headings
Adrenocortical Carcinoma, Peritoneal Neoplasms, Hyperthermia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Platinol

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

  • Cytoreductive surgeryProcedure or surgery

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

  • sodium thiosulfateDrug

    sodium thiosulfate will be given to limit the toxicity of cisplatin

Study groups in NCT01833832
Study groupRoleWhat they receive
Cytoreductive surgery followed by HIPECExperimentalCytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin
Receives: Drug: Cisplatin; Procedure: Cytoreductive surgery; Drug: sodium thiosulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Number of Patients With Treatment Related Morbidity Following the Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) Procedure

    Patients who died following the HIPEC procedure. The HIPEC is a surgical procedure in which two large bore catheters are inserted in the abdominal wall over the liver and pelvis. The physician closes the abdominal fascia and the catheters are connected to a perfusion circuit. The temperature of the catheters is carefully monitored while the physician ensures the perfusion is distributed properly by manually moving the abdomen.

    Measured: Patients were assessed every 3 months up to an average of 17 months.

  2. Percentage of Participants Who Survived 5-years Post Treatment

    Percentage of participants who are alive after treatment.

    Measured: 5 years

  3. 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

    QOL characteristics were collected using The Functional Assessment of Cancer Therapy-Colorectal Quality of Life (QOL) questionnaire version 4, a validated survey that interrogates physical, emotional, functional, and social well being in cancer related issues on a 5-point scale. Scores range from 0 to 108 points. Higher scores are consistent with a better outcome.

    Measured: Prior to surgery, 6 weeks post surgery, and 3 months post surgery

  4. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Measured: Date treatment consent signed to date off study, approximately 34 months and 28 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2013 (estimated)
  2. Study start12 Apr 2013
  3. Primary completion9 Aug 2018
  4. Study completion9 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01833832
Sponsor's protocol ID
130114
Other IDs
13-C-0114
Status last verified
Jul 2019
First submitted
12 Apr 2013
Last updated
30 Jul 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 22189845

  • 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.

    PubMed 20348273

  • 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.

    PubMed 14673042

  • 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.

    PubMed 30463745

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, Cytoreductive surgery and sodium thiosulfate in people with Adrenocortical Carcinoma and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intraperitoneal Progression Free Survival (PFS) (time frame: Amount of time subject survives without intraperitoneal disease progression after treatment, an average of 17 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01833832, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.

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