Study of DNA Mutations in Predicting the Effect of External-Beam Radiation Therapy in Patients With Early Breast Cancer, Localized Prostate Cancer, or Gynecological Cancer

Breast Cancer Clinical Trial

Official title:

Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy (RAPPER)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00601406
• Other study ID #: CDR0000581139
• Secondary ID: CHNT-RAPPEREU-20
• Status: Recruiting
• Phase: N/A
• First received: January 25, 2008
• Last updated: August 23, 2013
• Start date: March 2006

Study information

• Verified date: April 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This clinical trial is evaluating DNA mutations in predicting the effect of external-beam radiation therapy in patients with early breast cancer, localized prostate cancer, or gynecologic cancer.

Description:

OBJECTIVES:

Primary

• To test the hypothesis that an association between common genetic variations, reported by single nucleotide polymorphisms (SNP) in relevant candidate genes, is associated with individual patient variability in normal tissue radiation response and toxicity.

Secondary

• To compare different clinical scoring systems for late normal tissue effects, specifically Late Effect of Normal Tissue Subjective Objective Management Analysis (LENT SOMA), Radiation Therapy Oncology Group (RTOG), quality of life, and in a subset common terminology criteria (CTC) version 3.

• To compare clinical scoring systems with analytical measures of normal tissue outcome in a minority of patients, using volume change in the breast measured by laser camera.

• To correlate family history information with SNP analysis to produce a polymorphism risk score (PRS) for family history.

• To compare a detailed 3D dose-volume analysis in a subset of patients with late effects and SNP results.

• To correlate actuarial analysis of late effects changes over time with PRS.

• To conduct PRS analyses against tumor control probability (TCP), using survival as a surrogate for TCP where necessary, and normal tissue complications vs tumor control probability.

OUTLINE: This is a multicenter study.

Patients are recruited from clinical trials in which their late normal tissue effects have been measured. Blood samples are collected from these patients for analysis of genetic variation by DNA extraction and single nucleotide polymorphism analysis. Sixty different genes, including those involved in cell cycle checkpoint control, DNA damage recognition and repair, induction of apoptosis, and cytokine production (including TGFβ pathways) are assessed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2200
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Patients must have received curative external-beam radiotherapy within the context of a formal clinical study for any of the following:

• Early breast cancer after breast-conserving surgery

• Localized prostate cancer

• Gynecological cancer (may have also received brachytherapy)

• Venous blood samples must be available

• Patients will be identified from the following clinical studies:

• Cambridge intensity-modulated radiotherapy breast randomized trial

• RT01 prostate radiotherapy randomized trial/other prostate trials

• Christie hospital breast, prostate, and gynecological cancer radiotherapy patients

• Must have minimum follow up with late normal tissue effect scoring for two years available

PATIENT CHARACTERISTICS:

• No other malignancy prior to treatment for the specified tumor types except basal cell or squamous cell carcinoma of the skin or in situ carcinoma

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cervical Cancer
• Endometrial Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Sarcoma
• Uterine Cervical Neoplasms
• Vaginal Cancer
• Vaginal Neoplasms
• Vulvar Cancer
• Vulvar Neoplasms

Intervention

Genetic:
• gene expression analysis

• gene rearrangement analysis

• polymorphism analysis

Other:
• laboratory biomarker analysis

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Whiston Hospital	Prescot	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Southport and Formby District General Hospital	Southport	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Warrington Hospital NHS Trust	Warrington	England

Sponsors (1)

Lead Sponsor	Collaborator
Christie Hospital NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of association between common genetic variations, reported by single nucleotide polymorphisms (SNP) in relevant candidate genes, with individual patient variability in normal tissue radiation response and toxicity			No
Secondary	Comparison of different clinical scoring systems for late normal tissue effects			Yes
Secondary	Comparison of clinical scoring systems with analytical measures of normal tissue outcome using volume change in the breast measured by laser camera			Yes
Secondary	Correlation of family history information with SNP analysis to produce a polymorphism risk score (PRS)			No
Secondary	Comparison of detailed 3D dose-volume analysis with late effects and SNP results			No
Secondary	Correlation of actuarial analysis of late effects changes over time with PRS			No
Secondary	PRS analyses against tumor control probability (TCP), using survival as a surrogate for TCP where necessary, and normal tissue complications vs tumor control probability			No