Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer

NCT ID: NCT00981656

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2023-08-15

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.

Conditions

Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

3DCRT + CT

Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

60-minute intravenous (IV) infusion of 15 mg/m\^2 on days 1, 2, 3, 15, 16, 17, 29, 30, and 31 of radiation treatment.

5-fluorouracil

Intervention Type: DRUG

Continuous IV infusion of 500 mg/m\^2/24 hrs for 5 consecutive days during weeks 1 and 4 of radiation treatment.

Mitomycin

Intervention Type: DRUG

IV bolus dose of 12 mg/m\^2 on day 1 of radiation treatment.

Three-Dimensional Conformal Radiation Therapy

Intervention Type: RADIATION

Total dose to the gross bladder volume of 61.2 Gy as 34 daily fractions 5 days/week, for approximately 7 weeks.

Interventions

cisplatin

60-minute intravenous (IV) infusion of 15 mg/m\^2 on days 1, 2, 3, 15, 16, 17, 29, 30, and 31 of radiation treatment.

Intervention Type: DRUG

5-fluorouracil

Continuous IV infusion of 500 mg/m\^2/24 hrs for 5 consecutive days during weeks 1 and 4 of radiation treatment.

Intervention Type: DRUG

Mitomycin

IV bolus dose of 12 mg/m\^2 on day 1 of radiation treatment.

Intervention Type: DRUG

Three-Dimensional Conformal Radiation Therapy

Total dose to the gross bladder volume of 61.2 Gy as 34 daily fractions 5 days/week, for approximately 7 weeks.

Intervention Type: RADIATION

Other Intervention Names

5FU; 3DCRT; 3D CRT

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.

Exclusion Criteria

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William U. Shipley, MD, FACR

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Emory Crawford Long Hospital

Atlanta, Georgia, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Hudner Oncology Center at Saint Anne's Hospital - Fall River

Fall River, Massachusetts, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Beth Israel Medical Center - Petrie Division

New York, New York, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Barberton Citizens Hospital

Barberton, Ohio, United States

Cancer Care Center, Incorporated

Salem, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, United States

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

University of Texas Medical Branch

Galveston, Texas, United States

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, United States

Countries

United States

References

Dahl DM, Rodgers JP, Shipley WU, Michaelson MD, Wu CL, Parker W, Jani AB, Cury FL, Hudes RS, Michalski JM, Hartford AC, Song D, Citrin DE, Karrison TG, Sandler HM, Feng FY, Efstathiou JA. Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024 Dec;42(34):4095-4102. doi: 10.1200/JCO.23.02510. Epub 2024 Sep 3.

Reference Type: DERIVED

PMID: 39226514 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CDR0000654727

Identifier Type: -

Identifier Source: secondary_id

NCI-2011-01974

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG 0926

Identifier Type: -

Identifier Source: org_study_id