Rapid Autopsy and Procurement of Cancer Tissue

• ClinicalTrials.gov Identifier: NCT01851395
• Recruitment Status: Recruiting
• First Posted: May 10, 2013
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information

• First Submitted Date: May 8, 2013
• First Posted Date: May 10, 2013
• Last Update Posted Date: February 17, 2021
• Actual Study Start Date: December 30, 2013
• Estimated Primary Completion Date: March 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2021)

Tumor heterogeneity [ Time Frame: Death ]

Both intratumor and between paired primary and metastatic site, using integrated genomic and proteomic analysis.

• Original Primary Outcome Measures (submitted: May 8, 2013): Tumor tissue from multiple anatomical sites obtained [ Time Frame: within 3 hours after death ]

Current Secondary Outcome Measures (submitted: August 22, 2020)

Genetic alterations [ Time Frame: completion of study ]

To compare genetic alterations of autopsied tissue with archival tissue from primary and metastatic sites when available, to evaluate heterogeneity between primary and metastatic sites and at two different times during tumor evolution.Compare genomic alterations in tumor tissue with those identified in isolated circulating tumor cells from blood obtained during the short hospital stay before death.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rapid Autopsy and Procurement of Cancer Tissue
• Official Title: Inpatient Hospice With Procurement of Tissue on Expiration in Thoracic Malignancies, Bladder Cancer, Ovarian Cancer and Patients Treated With an Adoptive Cellular Therapy

Brief Summary

Background:

- Individuals with cancer of the lung, chest cavity, ovary, or bladder, as well as patients who have been treated with adoptive cell therapy unfortunately commonly succumb to their disease. Some agree to donate their bodies to cancer research that may help the medical community better understand these diseases. Studies of cancer tumor tissue obtained soon after death may be used to answer questions about the origins, progression, and treatment of cancer. Researchers want to conduct a study that involves planned collection of cancer tumor tissue shortly after death. To do so, they will arrange to provide inpatient hospice care for people with non-small cell lung cancer, ovarian cancer, bladder cancer, or patients who have been treated with adoptive cell therapy.

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Objectives:

- To collect cancer tissue biopsy samples as soon as possible after death.

Eligibility:

- Individuals who have cancer of the lung, chest cavity, ovary, or bladder, or those who have been treated with adoptive cell therapy and are planning to receive end-of-life hospice care are eligible to participate.

Design:

• Participants will agree to receive inpatient hospice care at the National Institutes of Health Clinical Center. Full details on end-of-life care preference will be acknowledged.
• An autopsy will be performed at the clinical center within 3 hours of death. Tumor tissue will be collected from the primary site of cancer and from any areas of the body to which the cancer has spread.
• Participants will not receive further cancer treatments as part of this study. This is a tissue collection study only....

Detailed Description

Background:

• Despite being the leading cause of cancer-related death worldwide, there is only limited knowledge of tumor heterogeneity in lung cancer. There is also limited knowledge of tumor heterogeneity of other less common thoracic malignancies, such as thymic epithelial tumors and mesothelioma. The extent and causes of intra-tumor and inter-metastatic heterogeneity in thoracic malignancies and how they compare to other tumor types is of utmost importance in managing lung cancer. Newer approaches of treating malignancies by targeting immune cells or tumor microenvironment are emerging. Adoptive cellular therapy (ACT) is one such approach. How this therapy affects individual metastatic sites and specific clones of tumor cells is poorly understood.
• Little is known about the clonal architecture of advanced, heavily-treated urothelial carcinoma or the dynamics that lead to metastasis and chemotherapy and immunotherapy resistance. Urothelial carcinomas have a high somatic mutation rate (median 5.5 per megabase) similar to that of non-small cell lung cancer and melanoma. Urothelial carcinoma tumors are extremely heterogenous and the extent of heterogeneity post treatment is an important area of research that should be further explored. Understanding the genetic and clonal evolution of urothelial carcinoma tumors will eventually help guide management of treatment-resistant metastatic tumors. Comprehensive tissue procurement by rapid autopsy will serve as a valuable mechanism to further characterize aggressive treatment-resistant, metastatic urothelial carcinomas and other rare genitourinary histologies.
• Ovarian carcinoma is frequently associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in ovarian cancer has not been elucidated. Despite prior efforts such as The Cancer Genome Atlas (TCGA) and other analyses that were predominantly focused on samples from patients who had upfront debulking surgery, an understanding of the molecular and cellular heterogeneity of ovarian cancer based on highly clinically annotated samples is lacking.
• Tumor heterogeneity can be evaluated in a comprehensive manner by deep sequencing and globally analyzing genomic and proteomic alterations of simultaneous core biopsies from several areas of the primary tumor and metastases. These analyses correlated with clinical outcomes can further the evaluation of tumor heterogeneity. However, such studies are not feasible in a clinical setting.
• Tissue procurement by rapid autopsies provides an effective way for such an investigation.

Hypothesis:

- Clonal evolution and selection of tumor cells can be assessed by examining genomic and proteomic alterations of tumor samples obtained from multiple sites of primary and metastatic sites.

Objectives:

- Procure primary and metastatic tissue of thoracic malignancies, ovarian cancer, bladder cancer and from patients treated with an ACT shortly after death, to investigate tumor heterogeneity and immune microenvironment intratumorally, between paired primary and metastatic sites, and among inter-metastatic tumors using integrated genomic and proteomic analysis.

Eligibility:

- Adult patients with metastatic non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), extrapulmonary small cell cancer (ESCC), pulmonary neuroendocrine tumor (pNET), thymic epithelial tumor, mesothelioma, bladder cancer (including urothelial carcinoma and other rare bladder or kidney histology), ovarian cancer, and patients treated with an ACT, with no expected chance of cure and an expected survival of less than 3 months.

Design:

• Forty patients with NSCLC; 30 each with SCLC, thymic epithelial tumors, and mesothelioma; 6 each of ESCC and pNET; 20 patients with bladder cancer; 20 patients with ovarian cancer; and 20 patients treated with an ACT will be autopsied in this study. The accrual ceiling for the study will be set at 205 in order to account for subjects that for whatever reason do not undergo autopsy.
• Patients will be admitted for inpatient hospice when an investigator evaluates that death is clinically imminent.
• Upon expiration, rapid autopsy will be performed and tissue will be obtained from the primary tumor site, if identifiable, and multiple metastatic sites to assess tumor heterogeneity and immune microenvironment using deep sequencing and global genomic and proteomic analyses.
• Archival tissue from patients, if available, will be used to evaluate these changes from several stages of tumor progression.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients will be selected primarily from the CC medical oncology clinic setting.

Condition

• Thymus Tumors
• Adoptive Cellular Therapy
• Mesothelioma
• Genitourinary Cancers
• Lung Cancers

• Intervention: Not Provided

Study Groups/Cohorts

• 1/Thoracic malignancies
  Patients with histologically or cytologically confirmed metastatic NSCLC, SCLC, EPCC, pNET, thymic epithelial tumor (thymoma, thymic carcinoma) or mesothelioma.
• 2/Genitourinary malignancies
  Patients with genitourinary malignancies
• 3/ACT
  Patients treated with an adoptive cellular therapy
• 4/Ovarian
  Patients with ovarian cancer

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2021): 205
• Original Estimated Enrollment (submitted: May 8, 2013): 12
• Estimated Study Completion Date: March 31, 2027
• Estimated Primary Completion Date: March 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:
• Patients must have histologically or cytologically confirmed metastatic NSCLC, SCLC, EPCC, pNET, thymic epithelial tumor (thymoma, thymic carcinoma) or mesothelioma confirmed by the NCI Laboratory of Pathology. Patients with bladder cancer (including urothelial carcinoma and other rare bladder or kidney histology), ovarian cancer, and malignancies previously treated with an ACT are also eligible.
• Age >= 18 years.
• Incurable disease or terminal diagnosis
• Patients or legally authorized representative (LAR) must sign an informed consent indicating that they are aware of the investigational nature of this study.
• Patients must provide valid written designation of an assigned Durable Power of Attorney (DPA). If one is not available, an LAR must be assigned.
• Patients and their legal next of kin must agree to a Do Not Resuscitate (DNR) order and agree to Consent for Autopsy as part of the end-of-life care plan.
• This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate

EXCLUSION CRITERIA:

• Women known to be pregnant (known positive pregnancy test, although such testing is not required for enrollment) are excluded.
• Known HIV-positive patients will be excluded (although HIV testing is not required for enrollment) because of the potential for contamination of tissue.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Linda C Sciuto, R.N.; (240) 760-6117; lsciuto@mail.nih.gov

Contact: Anish Thomas, M.D.; (240) 760-7343; anish.thomas@nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01851395
• Other Study ID Numbers: 130131; 13-C-0131
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anish Thomas, M.D.; National Cancer Institute (NCI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: February 6, 2021