Genetic Susceptibility and Risk of Second Cancers in Patients Who Have Undergone Stem Cell Transplant for Cancer

Cancer Clinical Trial

Official title:

Radiation Sensitivity, DNA Repair, and Second Cancers.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00949052
• Other study ID #: VICC REACH 0901
• Secondary ID: P30CA068485FHCRC
• Status: Terminated
• Start date: January 2009
• Est. completion date: February 2018

Study information

• Verified date: August 2018
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

RATIONALE: Identifying genes that increase a person's susceptibility to second cancers may help the study of cancer treatment.

PURPOSE: This study is looking at genetic susceptibility and risk of second cancers in patients who have undergone stem cell transplant for cancer.

Description:

OBJECTIVES:

Primary

• Determine whether genetic susceptibility (e.g., inherited differences in radiation sensitivity to normal tissue or genes of xenobiotic metabolism, nucleotide provision, or DNA repair) to the carcinogenic effects of radiotherapy, tobacco, and UV light modifies the risk of second malignant neoplasms (SMN) in patients with cancer treated with hematopoietic stem cell transplantation (HSCT).

Secondary

• Measure inherent sensitivity to radiotherapy via G_2 chromosome radiation sensitivity assay using B-cell lymphoblastoid cell lines derived from pre-HSCT cryopreserved peripheral blood mononuclear cells of patients with and without SMN.

• Measure the frequency of allelic variants of genes involved in xenobiotics metabolism, DNA repair, and provision of nucleotide pool and compare the frequencies among patients with and without SMN, determine the transmission of specific alleles of these genes from parents to patients, and correlate allelic variants of DNA repair and nucleotide provision in genes with in vitro radiation sensitivity.

• Evaluate the role of potentially carcinogenic environmental exposures (tobacco and sun light) pre- or post-HSCT in the risk of SMN and examine the association of these exposures with SMN and the interaction of these exposures with allelic variants of genes involved in xenobiotic metabolism, nucleotide provision, and DNA repair.

OUTLINE: Patients complete self-reported questionnaires and medical records are reviewed to collect information on UV light and tobacco exposure pre- and post-transplantation. Information is analyzed for association with second malignancy neoplasms.

Blood samples are collected from patients pre-hematopoietic stem cell transplantation and from their parents (when available) or other first-degree relatives for genetic biomarkers of susceptibility to second malignancies, DNA repair and provision nucleotide, genetic susceptibility to toxicity from combined cancer therapies, and environmental carcinogens.

PROJECTED ACCRUAL: A total of 1,000 patients (800 patients without second malignant neoplasms [SMN] and 200 patients with SMN) will be accrued for this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1000
• Est. completion date: February 2018
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

CASES are those who:

• Survived at least 100 days post-hematopoietic stem cell transplantation (HSCT).

• Developed an SMN after that time point.

• And received TBI as part of the preparative regimen.

CONTROLS are randomly selected:

• In a 4:1 ratio to cases from the same cohort of 100 day + survivors of HSCT who received TBI.

• Controls will be matched to the cases by race and primary diagnosis.

• In addition, they must have survived for at least the elapsed time between the case's HSCT and the secondary cancer, without development of an SMN.

• We are matching on primary diagnosis, as genotype or radiation sensitivity may predispose to specific primary cancers, as well as the SMNs.

• We are matching on race, as allele frequencies vary widely across ethnic groups.

Exclusion Criteria:

• Did not survive at least 100 days post-hematopoietic stem cell transplantation (HSCT).

• Did not develop an SMN after that time point.

• Did not receive TBI as part of the preparative regimen.

Related Conditions & MeSH terms

• Cancer
• Neoplasms, Second Primary

Intervention

Genetic:
• DNA analysis

• polymorphism analysis

Other:
• laboratory biomarker analysis

• medical chart review

• questionnaire administration

Procedure:
• assessment of therapy complications

• evaluation of cancer risk factors

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic susceptibility to the carcinogenic effects of radiotherapy, tobacco, and UV light and risk of second malignant neoplasms (SMN)		At study entry
Secondary	Radiation sensitivity in B-cell lymphoblastoid cells		At study entry
Secondary	Allelic variants of genes involved in xenobiotics metabolism, DNA repair, and provision of nucleotide pool of patients with SMN compared to their first-degree relatives and patients without SMN		At study entry
Secondary	Role of potentially carcinogenic environmental exposures (tobacco and sun light) pre- and post-HSCT in the risk of SMN		At study entry