Severe or Mild Toxicity From Radiotherapy and/or Chemotherapy Clinical Trial
Official title:
Mechanisms and Predictors of Unusual Radiation or Chemotherapy Toxicity
| NCT number | NCT02469194 |
| Other study ID # | UPCC 09915 |
| Secondary ID | |
| Status | Withdrawn |
| Phase | |
| First received | |
| Last updated | |
| Start date | June 2015 |
| Est. completion date | June 2020 |
| Verified date | September 2019 |
| Source | Abramson Cancer Center of the University of Pennsylvania |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | June 2020 |
| Est. primary completion date | June 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Adverse Events | 5 years |