Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer

NCT00055601 | Completed Phase 2 Results DMC

• 4 other identifiers: RTOG 0233CDR0000258303ECOG-R0233NCI-2011-01578
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of combination chemotherapy plus radiation therapy with or without surgery is more effective in treating bladder cancer. PURPOSE: Randomized phase II trial to study the effectiveness of two combination chemotherapy regimens and radiation therapy with or without radical cystectomy in treating patients who have stage II or stage III bladder cancer.

Conditions

Bladder Cancer

Keywords

stage II bladder cancer; stage III bladder cancer

Outcome Measures

Primary Outcomes (1)

• Treatment Completion Rate

  Radiation therapy and chemotherapy per protocol or within acceptable variation guidelines based on central review. The study was designed for a two-sided binomial test with 87% power and a significance level of 0.05 with a null hypothesis of a 70% completion rate against the alternative 90% completion rate. For each arm, more than 34 out of 43 evaluable patients completing the treatment, would indicate to reject the null hypothesis for a better treatment completion rate. Fewer than 24 out 43 evaluable patients completing the treatment would indicate to reject the null hypothesis for a worse treatment completion rate. Otherwise, the conclusion would be that there is not enough evidence to reject the null hypothesis of a 70% completion rate in either direction.

  From randomization to 11 weeks

Secondary Outcomes (2)

• Complete Response After Induction

  From randomization to eight weeks

• Bladder-intact Survival Rate (5 Years)

  From the date of randomization to five years.

Study Arms (2)

Pelvic RT + paclitaxel + cisplatin

EXPERIMENTAL

Induction: Twice-daily pelvic radiation therapy (RT) with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin.

Drug: cisplatin; Drug: paclitaxel; Radiation: radiation therapy; Drug: Gemcitabine; Procedure: Radical cystectomy

Pelvic RT + fluorouracil + cisplatin

EXPERIMENTAL

Induction: Twice-daily pelvic radiation therapy (RT) with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin.

Drug: cisplatin; Drug: fluorouracil; Radiation: radiation therapy; Drug: Gemcitabine; Procedure: Radical cystectomy

Interventions

cisplatin DRUG

Induction: 15 mg/m2 as a 60-minute infusion on days 1, 2, 3, 8, 9, 10, 15, 16, and 17; Consolidation: 15 mg/m2 as a 60-minute infusion on days 1, 2, 8, and 9; Adjuvant: 35 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.

Pelvic RT + fluorouracil + cisplatin; Pelvic RT + paclitaxel + cisplatin

fluorouracil DRUG

Induction: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 15, 16, and 17; Consolidation: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 8, 9, and 10.

Pelvic RT + fluorouracil + cisplatin

paclitaxel DRUG

Induction: 50 mg/m2 as a 60-minute infusion on days 1, 8, and 15; Consolidation: 50 mg/m2 as a 60-minute infusion on days 1 and 8; Adjuvant: 50 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.

Pelvic RT + paclitaxel + cisplatin

radiation therapy RADIATION

Induction: External beam irradiation, 1.6 Gy, will be given to the pelvis in the first treatment followed by an interfraction period of at least 4-6 hours. During the second treatment, 1.5 Gy will be delivered to the whole bladder for the first five sessions (7.5 Gy) then to the tumor plus a margin for eight sessions (12. Gy). Consolidation: Consolidation therapy will start 7-14 days following a cystoscopic re-evaluation demonstrating a complete response to the induction therapy. 1.5 Gy (per fraction) will be given to the pelvis in two treatment fractions per day, with an interfraction period of at least 4-6 hours.

Pelvic RT + fluorouracil + cisplatin; Pelvic RT + paclitaxel + cisplatin

Gemcitabine DRUG

Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.

Pelvic RT + fluorouracil + cisplatin; Pelvic RT + paclitaxel + cisplatin

Radical cystectomy PROCEDURE

Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.

Pelvic RT + fluorouracil + cisplatin; Pelvic RT + paclitaxel + cisplatin

Eligibility Criteria

• Age: Up to 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed operable primary muscle invasive bladder cancer * T2-T4a, NX or N0, M0 (stage II or III) * Must have an adequate functioning bladder * Must have undergone a prior transurethral resection of the bladder tumor within the past 8 weeks * No evidence of tumor-related hydronephrosis * No evidence of distant metastases or histologically or cytologically confirmed lymph node metastases * Patients with involvement of the prostatic urethra with transitional cell cancer that was visibly completely resected are allowed * No evidence of stromal invasion of the prostate PATIENT CHARACTERISTICS: Age * Not specified Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Hemoglobin at least 10 g/dL * White blood cell (WBC) count at least 4,000/mm\^3 * Absolute neutrophil count at least 1,800/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic * Serum bilirubin no greater than 2.0 mg/dL Renal * Serum creatinine no greater than 1.5 mg/dL * Creatinine clearance at least 60 mL/min NOTE: If the creatinine clearance is greater than 60 mL/min, creatinine of no greater than 1.8 mg/dL is allowed at the discretion of the study chair Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy within the past 5 years except nonmelanoma skin cancer, stage T1a prostate cancer, or carcinoma in situ of the cervix * Must be able to tolerate systemic chemotherapy with pelvic radiotherapy and radical cystectomy PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior systemic chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior pelvic radiotherapy Surgery * See Disease Characteristics Other * No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycosides)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• Eastern Cooperative Oncology Group: collaborator
• NRG Oncology: collaborator

Study Sites (2)

LDS Hospital

Salt Lake City, Utah, 84103, United States

Location

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, 84106, United States

Location

Related Publications (2)

• Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. doi: 10.1200/JCO.2014.57.5548. Epub 2014 Nov 3.

  PMID: 25366678 DERIVED

• Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.

  PMID: 23823157 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; Fluorouracil; Paclitaxel; Radiotherapy; Gemcitabine; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Anthony L. Zietman, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Robert Uzzo, MD

  Fox Chase Cancer Center

  STUDY CHAIR

• Robert Dreicer, MD, FACP

  The Cleveland Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2003
• First Posted: March 7, 2003
• Study Start: December 1, 2002
• Primary Completion: October 1, 2010
• Study Completion: May 14, 2018
• Last Updated: June 15, 2018
• Results First Posted: August 10, 2016

Record last verified: 2018-05

Locations

US (2)