Surgery and Heated Chemotherapy for Adrenocortical Carcinoma

Learn more about:
Related Clinical Trial
Natural History Study of Children and Adults With Adrenocortical Cancer (ACC) Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors Combination Chemotherapy With Suramin Plus Doxorubicin in Treating Patients With Advanced Solid Tumors Natural History Study of Infants With Adrenal Masses Found on Prenatal and/or Neonatal Imaging Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor International Pediatric Adrenocortical Tumor Registry Antineoplaston Therapy in Treating Patients With Stage IV Adrenal Gland Cancer Structured Evaluation of adRENal Tumors Discovered Incidentally – Prospectively Investigating the Testing Yield Evaluation of 123I-Iodometomidate for Adrenal Scintigraphy Sorafenib Plus Paclitaxel in Adreno-Cortical-Cancer Patients Efficacy of Adjuvant Mitotane Treatment (ADIUVO) Possible New Therapy for Advanced Cancer IMC-A12 With Mitotane vs Mitotane Alone in Recurrent, Metastatic, or Primary ACC That Cannot Be Removed by Surgery Studying Genes in Samples From Younger Patients With Adrenocortical Tumor Single Agent Pembrolizumab in Subjects With Advanced Adrenocortical Carcinoma Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery Evaluation of Side Effects of Mitotane Optimal Methods of Disease Progression and Survival Analysis in Children and Adults Patients With Adrenocortical Cancer (ACC) Surgery and Heated Chemotherapy for Adrenocortical Carcinoma Sunitinib in Refractory Adrenocortical Carcinoma Nivolumab in Treating Patients With Metastatic Adrenocortical Cancer Phase II Study for Combination of Camrelizumab and Apatinib in the Second-line Treatment of Recurrent or Metastatic Adrenocortical Carcinoma Phase 1 Study of ATR-101 in Subjects With Advanced Adrenocortical Carcinoma Treatment Study Using Bevacizumab for Patients With Adrenocortical Carcinoma Adjuvant Chemotherapy vs. Observation/Mitotane After Primary Surgical Resection of Localized Adrenocortical CarcInoma A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma S9427, Suramin in Treating Patients With Stage III or Stage IV Adrenocortical Cancer Incurable by Surgery Natural History and Tissue Acquisition Study of Adrenocortical Carcinoma Cabozantinib in Advanced Adrenocortical Carcinoma Trial With Taxotere and Cisplatin in Non-operable Adrenocortical Carcinoma German Adrenocortical Carcinoma Registry Clinical Trial of Dovitinib in First-line Metastatic or Locally Advanced Non-resectable Adrenocortical Carcinoma

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