Clinical trial NCT01124682: 3-Dimensional Conformal Radiation Therapy in Treating Patients With Bladder Cancer Who Have Undergone Transurethral Resection of the Bladder
Official title: Image Guided Dose Escalated Adaptive Bladder Radiotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Bladder Cancer
Keywords: adenocarcinoma of the bladder
squamous cell carcinoma of the bladder
transitional cell carcinoma of the bladder
recurrent bladder cancer
stage II bladder cancer
stage III bladder cancer
stage IV bladder cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-05-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase I trial is studying the side effects and best dose of 3-dimensional conformal radiation therapy in treating patients with bladder cancer who have undergone transurethral resection of the bladder.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum-tolerated dose of external-beam radiotherapy delivered as a tumor boost in patients who have undergone prior transurethral bladder resection for muscle-invasive carcinoma of the bladder.

Secondary

* To document progression-free survival and overall survival of these patients.
* To evaluate patterns of recurrence and bladder preservation rates following dose-escalated radiotherapy in these patients.
* To determine the impact of acute and late toxicity on quality of life in these patients.
* To assess the use of gold seeds for tumor boost delineation in these patients.
* To evaluate the use of virtual cystoscopy tumor localization in these patients.
* To assess coverage of the phase II radiotherapy boost volume on the daily cone-beam images.
* To assess coverage of the phase III radiotherapy volume on cone-beam images with selected adaptive strategy.
* To evaluate the use of diffusion-weighted MRI (dwMRI) scans in assessing response to radiotherapy.

OUTLINE: This is a dose-escalation study.

Patients undergo a rigid cystoscopy and gold-seed insertion, if clinically appropriate. Approximately 3-5 seeds are inserted into the bladder wall to demarcate the maximum extent of visible tumor or tumor bed via a customized introducer. All patients undergo 3-dimensional conformal radiotherapy once daily, 5 days per week during weeks 1 and 4-7 and once daily, 4-6 days per week during weeks 2 and 3, using a combination of image-guided radiotherapy techniques and a partial bladder radiotherapy boost.

Patients complete quality-of-life questionnaire QOL-30 at baseline, 1 and 3 months, and then annually after completion of study treatment.

After completion of study treatment, patients are followed up at 4, 8, and 12 weeks, every 6 months for 3 years, and then annually for 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed invasive bladder carcinoma, including the following cellular types:

  * Adenocarcinoma
  * Transitional cell carcinoma
  * Squamous cell carcinoma
* Clinical stage G1-3, pT2a-4 disease

  * Localized disease
  * No bone or visceral metastases
  * No lymph node metastases
* Has undergone maximal transurethral resection of the bladder tumor and planning to receive radical radiotherapy

PATIENT CHARACTERISTICS:

* WHO performance status 0-1
* Hemoglobin \> 10 g/dL
* WBC \> 3,000/mm\^3
* Platelet count \> 150,000/mm\^3
* Creatinine \< 120 μmol/L
* Bilirubin \< 1.5 times upper limit normal (ULN)
* AST \< 1.5 times ULN
* Alkaline phosphatase \< 1.5 times ULN
* Not pregnant
* No inflammatory bowel disease or other significant small bowel disease
* Physically fit for radical radiotherapy
* No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* No other malignancy within the past 2 years except adequately treated basal cell carcinoma of the skin or adequately treated carcinoma in situ of the cervix uteri

  * Prior superficial transitional cell carcinoma of the bladder allowed

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior pelvic surgery
* No bilateral hip replacements compromising accurate radiotherapy planning
* No prior radiotherapy to the pelvis

Primary outcomes:
measure: Maximum-tolerated dose
Secondary outcomes:
measure: Progression-free survival
measure: Overall survival
measure: Bladder preservation rates
measure: Acute and late toxicity and safety profile
measure: Quality of life
measure: Tumor boost volumes delineated with and without gold seeds
measure: Dose-volume histogram analysis of PTV2 and PTV3 coverage
measure: Change in diffusion coefficient between pre- and post-radiotherapy dwMRI scans
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Robert A. Huddart, MD
role: PRINCIPAL_INVESTIGATOR
References: