Clinical trial NCT00601406: 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
Official title: Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy (RAPPER)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Cervical Cancer
Endometrial Cancer
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Prostate Cancer
Sarcoma
Vaginal Cancer
Vulvar Cancer
Keywords: male breast cancer
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IA cervical cancer
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
stage I vaginal cancer
stage II vaginal cancer
stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
stage IA vulvar cancer
stage IB vulvar cancer
stage II vulvar cancer
stage IIIC vulvar cancer
stage IIIA vulvar cancer
stage IIIB vulvar cancer
stage IVB vulvar cancer
stage IA ovarian epithelial cancer
stage IB ovarian epithelial cancer
stage IC ovarian epithelial cancer
stage IA ovarian germ cell tumor
stage IB ovarian germ cell tumor
stage IC ovarian germ cell tumor
stage IIA ovarian epithelial cancer
stage IIB ovarian epithelial cancer
stage IIC ovarian epithelial cancer
stage IIA ovarian germ cell tumor
stage IIB ovarian germ cell tumor
stage IIC ovarian germ cell tumor
stage IIIA ovarian epithelial cancer
stage IIIB ovarian epithelial cancer
stage IIIC ovarian epithelial cancer
stage IIIA ovarian germ cell tumor
stage IIIB ovarian germ cell tumor
stage IIIC ovarian germ cell tumor
stage IV ovarian epithelial cancer
stage IV ovarian germ cell tumor
stage II endometrial carcinoma
ovarian stromal cancer
ovarian sarcoma
stage IA fallopian tube cancer
stage IB fallopian tube cancer
stage IC fallopian tube cancer
stage IIA fallopian tube cancer
stage IIB fallopian tube cancer
stage IIC fallopian tube cancer
stage IIIA fallopian tube cancer
stage IIIB fallopian tube cancer
stage IIIC fallopian tube cancer
stage IV fallopian tube cancer
recurrent primary peritoneal cavity cancer
stage IA primary peritoneal cavity cancer
stage IB primary peritoneal cavity cancer
stage IC primary peritoneal cavity cancer
stage IIA primary peritoneal cavity cancer
stage IIB primary peritoneal cavity cancer
stage IIC primary peritoneal cavity cancer
stage IIIA primary peritoneal cavity cancer
stage IIIB primary peritoneal cavity cancer
stage IIIC primary peritoneal cavity cancer
stage IV primary peritoneal cavity cancer
stage IA endometrial carcinoma
stage IB endometrial carcinoma
stage IIIA endometrial carcinoma
stage IIIB endometrial carcinoma
stage IIIC endometrial carcinoma
stage IVA endometrial carcinoma
stage IVB endometrial carcinoma
stage IA uterine sarcoma
stage IB uterine sarcoma
stage IC uterine sarcoma
stage IIA uterine sarcoma
stage IIB uterine sarcoma
stage IIIA uterine sarcoma
stage IIIB uterine sarcoma
stage IIIC uterine sarcoma
stage IVA uterine sarcoma
stage IVB uterine sarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-01-28
Enrollment: 2200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
Secondary outcomes:
measure: Comparison of different clinical scoring systems for late normal tissue effects
measure: Comparison of clinical scoring systems with analytical measures of normal tissue outcome using volume change in the breast measured by laser camera
measure: Correlation of family history information with SNP analysis to produce a polymorphism risk score (PRS)
measure: Comparison of detailed 3D dose-volume analysis with late effects and SNP results
measure: Correlation of actuarial analysis of late effects changes over time with PRS
measure: PRS analyses against tumor control probability (TCP), using survival as a surrogate for TCP where necessary, and normal tissue complications vs tumor control probability
Other outcomes:
Locations:
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Prescot
country: United Kingdom
facility: Whiston Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southport
country: United Kingdom
facility: Southport and Formby District General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Warrington
country: United Kingdom
facility: Warrington Hospital NHS Trust
state: England
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Catherine West
role: STUDY_CHAIR
References: