Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT01851395 |
| Other study ID # |
130131 |
| Secondary ID |
13-C-0131 |
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 30, 2013 |
Study information
| Verified date |
June 3, 2024 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
Linda C Sciuto, R.N. |
| Phone |
(240) 760-6117 |
| Email |
linda.sciuto[@]nih.gov |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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 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....
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 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.
- 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.
- There is a major need for effective immunotherapies against the common epithelial
cancers that account for the vast majority of cancer deaths. Even for lung cancer, where
checkpoint inhibition has some efficacy, the majority of these patients do not respond.
One option to address these cancers is the adoptive transfer of tumor reactive T-cells
(Adoptive Cell Therapy, ACT), which has already demonstrated durable complete cancer
regression in a few cases. This approach requires ways to either enrich for
tumor-reactive T-cells from tumor infiltrating lymphocytes (TIL) or to rapidly clone
mutation-reactive T-cell receptors and use them to engineer T-cell populations for
administration. The T-cell response to tumor specific mutations (neoantigens) is highly
patient specific and greatly affected by tumor heterogeneity. Developing better ways to
d select TIL and TCR for clinical use are needed to advance ACT.
- 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.
Objectives:
- Procure primary and metastatic tissue of thoracic malignancies, ovarian cancer, bladder
cancer, epithelial cancer (breast, colorectal, pancreatic, stomach or biliary cancers) 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, immunologic 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, epithelial cancer and patients
treated with an ACT, with no expected chance of cure and an expected survival of less than 3
months.
Design:
- The accrual ceiling for the study will be set at 275 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.
