Clinical trial NCT00981656: Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
Official title: A Phase II Protocol for Patients With Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent With Radiosensitizing Chemotherapy Following a Thorough Transurethral Surgical Re-Staging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: stage I bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2009-09-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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. Drugs used in chemotherapy, such as cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy given together with chemotherapy works in treating patients with stage I bladder cancer.

Detailed description: After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and annually thereafter until termination of the study.

Eligibility criteria: Inclusion criteria

1. Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to registration.

   • Operable patients whose initial tumor is a primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis; patients who have involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate remain eligible. If the patient's initial tumor was a high grade stage Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible.
2. Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days after completion of the initial treatment \[TURBT and intravesical Bacillus Calmette Guerin (BCG) immunotherapy\] or on initial presentation with a T1 high grade tumor, the participating urologist judged BCG therapy is contraindicated or unsuitable because the patient is found to be intolerant of BCG therapy or because this patient may be immuno-compromised in ways other than that mentioned in Exclusion Criteria 2.8 or because the patient refuses BCG therapy.
3. With the presentations as described in Section 2, the participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy.
4. If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or by percutaneous needle biopsy. Patients with histologically or cytologically confirmed node metastases will not be eligible.
5. Patients must have an adequately functioning bladder as judged by the participating urologist and radiation oncologist and have undergone a re-staging TURBT by the participating urologist that showed (or was present in the outside pathology specimen) a high grade stage Ta or T1 tumor with uninvolved muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy in the prostatic stroma of tumor invasion.
6. Patient must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy (if necessary) by the joint agreement of the participating urologist, radiation oncologist, and medical oncologist.
7. Appropriate stage for protocol entry, based upon the following minimum diagnostic workup within 60 days prior to registration:

   • History/physical examination including weight, performance data, body surface area
8. Zubrod Performance Status ≤ 1
9. Age ≥ 18
10. Complete blood count (CBC)/differential obtained no more than 30 days prior to registration on study, with adequate bone marrow function defined as follows:

    * White blood cell count (WBC) ≥ 4,000/ml
    * Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3
    * Platelets ≥ 100,000 cells/mm3
    * Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.)
11. If the patient is to be treated with cisplatin, the serum creatinine should be ≤ 1.5 mg%; serum bilirubin of ≤ 2.0 mg%
12. Glomerular filtration rate (GFR) \> 25 ml/min \[For patients receiving cisplatin, GFR ≥ 60 ml/min\]
13. Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior to study entry; women of childbearing potential and male participants must practice adequate contraception.
14. Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria

1. Evidence of tumor-related hydronephrosis
2. Evidence of distant metastases or histologically or cytologically proven lymph node metastases
3. Prior systemic chemotherapy for bladder cancer; prior chemotherapy for a different cancer is allowable
4. A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix or a urothelial carcinoma of the upper urinary tract stage pTa, pTis or pT1 that has not been free of disease after treatment for more than a 2-year period
5. Patients with pN+ or \> T1 disease or who have not had a visibly complete TURBT
6. Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)
7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
8. Severe, active co-morbidity, defined as follows:

   * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
   * Transmural myocardial infarction within the last 6 months;
   * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
   * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
   * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
   * Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
9. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
10. Prior allergic reaction to the study drugs (cisplatin, mitomycin, 5FU) involved in this

Primary outcomes:
measure: Percentage of Participants Free From Radical Cystectomy at 3 Years
timeFrame: Three years from registration
Secondary outcomes:
measure: Percentage of Participants Free From Radical Cystectomy at 5 Years
timeFrame: Five years from registration
measure: Percent of Participants With Distant Disease Progression at 3 Years
timeFrame: From registration to three years
measure: Percent of Participants With Distant Disease Progression at 5 Years
timeFrame: From registration to five years
measure: Percentage of Participants With Progression to Tumor Stage T2 or Greater at 3 Years
timeFrame: From registration to three years
measure: Percentage of Participants With Progression to Tumor Stage T2 or Greater at 5 Years
timeFrame: From registration to five years
measure: Percentage of Participants Who Have Died From Bladder Cancer at 5 Years (Disease-specific Survival)
timeFrame: From registration to five years
measure: Percentage of Participants Alive at 3 Years
timeFrame: From registration to three years
measure: Percentage of Participants Alive at 5 Years
timeFrame: From registration to five years
measure: Distribution of Participants by Highest Grade Adverse Event
timeFrame: Adverse events are evaluated 8-10 weeks after end of study treatment (approximately 7 weeks), then every 3 months for one year, every 4 months for one year, every 6 months for 3 years, then annually. Maximum follow-up at time of reporting was 8.6 years.
measure: Percentage of Participants With Local Recurrence at 3 Years
timeFrame: From registration to three years
measure: American Urological Association Total Symptom Score at Baseline and at 3 Years
timeFrame: Baseline and 3 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Fall River
country: United States
facility: Hudner Oncology Center at Saint Anne's Hospital - Fall River
state: Massachusetts
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Beth Israel Medical Center - Petrie Division
state: New York
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center - North
state: Vermont
Study officials:
affiliation: Massachusetts General Hospital
name: William U. Shipley, MD, FACR
role: PRINCIPAL_INVESTIGATOR
References: