Mechanisms and Predictors of Unusual Radiation or Chemotherapy Toxicity

NCT ID: NCT02469194

Last Updated: 2019-09-11

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2020-06-30

Brief Summary

In general, the toxicity of radiation therapy and chemotherapy exhibits a strong dose-response relationship. However, patients receiving similar doses still exhibit a range of toxicity responses due to a variety of factors, including comorbid conditions, disease (cancer) specific factors, and inter-individual genetic variation. A very small percentage of patients experience side effects that are either extremely severe or extremely mild compared to the majority of patients for the dose of radiation or chemotherapy given. Currently, the reasons for this are not entirely clear, but likely relate to patient specific factors such as immune response, cell/tissue repair capacity and other factors that fundamentally rely on rare genetic variations at loci involved in these responses. For example, patients with homozygous deletions in DNA damage response genes such as ATM are uniquely sensitive to DNA damaging agents. Many patients with severe, homozygous mutations in such genes have other sequela that lead to medical recognition of the syndrome prior to therapy. The investigators hypothesize that patients with unusually severe toxicity from therapy that do not exhibit classical signs of homozygous mutation syndromes are heterozygous for nonfunctional or hypofunctional alleles at these loci, such that the defect is only uncovered under the relatively acute, severe stress on that pathway by radiation or chemotherapy. Conversely, patients with very mild reactions could exhibit rare variants/combinations of variants that make them uniquely resistant to chemotherapy or radiotherapy toxicity.

The purpose of the study is to better understand these mechanisms with the eventual goal of developing predictive markers that will allow us to help individually tailor cancer therapy is in future patients. Will accomplish these goals by studying a variety of factors from a single vial of blood. These will include circulating proteins and hormones, circulating cells and the levels and sequences of white blood cell DNA or RNA using a variety of techniques including but not limited to determination of cytokine/hormone levels, proteomic analysis, immunocytochemical assays, whole exome sequencing and qPCR.

Conditions

Severe or Mild Toxicity From Radiotherapy and/or Chemotherapy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Blood Draw

5-10 cc of whole blood will be obtained using standard, sterile venipuncture techniques

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects will be age 18 or greater Subjects will have undergone chemotherapy and/or radiotherapy and experienced unusually mild or severe toxicity.

Exclusion Criteria

• Subjects for who, after initial review of medical records by study team personnel are not judged by the PI and/or sub-investigators to have sufficiently unusual toxicity from therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keith Cengel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

UPCC 09915

Identifier Type: -

Identifier Source: org_study_id