Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery
A Phase II Randomized Study For Patients With Muscle-Invasive Bladder Cancer Evaluating Transurethral Surgery And Concomitant Chemoradiation By Either BID Irradiation Plus 5-Fluorouracil And Cisplatin Or QD Irradiation Plus Gemcitabine Followed By Selective Bladder Preservation And Gemcitabine/Cisplatin Adjuvant Chemotherapy
2 other identifiers
interventional
70
2 countries
11
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2008
Longer than P75 for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 21, 2008
CompletedFirst Posted
Study publicly available on registry
October 22, 2008
CompletedStudy Start
First participant enrolled
December 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 18, 2018
CompletedResults Posted
Study results publicly available
August 21, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2022
CompletedJune 15, 2022
May 1, 2022
9.2 years
October 21, 2008
May 31, 2019
May 23, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Patients Without Distant Metastases by Three Years
Distant metastasis occurrence is defined as the first appearance of disease (with radiographic evidence) in a non-regional lymph node, solid organ or bone.
From randomization to three years
Secondary Outcomes (7)
Percentage of Patients Who Completed Treatment Per Protocol
After each treatment component (induction, consolidation, adjuvant). Timing varies bases on arm, tumor response at multiple time points, and allowed time ranges.
Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events
From start of treatment to 180 days after the end of treatment. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges.
Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy
3-4 weeks following induction therapy (approximately maximum 8 weeks from start of treatment depending on treatment arm and allowed time windows)
Number of Participants With Progression or Removal of Bladder Five Years After Therapy
From start of treatment to five years after the end of therapy. Treatment could last up to 40 weeks depending on arm, tumor response, and allowed time ranges.
Change in American Urological Association Symptom Index (AUASI) Score at 3 Years
Baseline and 3 years
- +2 more secondary outcomes
Study Arms (2)
5-FU and Cisplatin + BID Irradiation
EXPERIMENTALWithin 8 weeks following pre-study transurethral resection (TUR) patients receive 2.5 weeks of induction chemoradiotherapy (induction 5-fluorouracil, induction cisplatin, induction BID radiation therapy). Consolidation chemoradiotherapy begins 7-14 days following post-induction chemoradiotherapy endoscopic response evaluation. Patients achieving a complete response receive 1.5 weeks of consolidation chemoradiotherapy (consolidation 5-fluorouracil, consolidation cisplatin, consolidation BID radiation therapy). Patients without a complete response undergo radical cystectomy. Outpatient adjuvant chemotherapy (adjuvant gemcitabine, adjuvant cisplatin) begins 4-5 weeks following the post-consolidation endoscopic evaluation or 8-12 weeks following radical cystectomy, and continues for 12 weeks.
Gemcitabine + QD Irradiation
EXPERIMENTALWithin 8 weeks following pre-study transurethral resection (TUR) patients receive 2.5 weeks of induction chemoradiotherapy (induction gemcitabine and induction QD radiation therapy). Consolidation chemoradiotherapy begins 7-14 days following post-induction chemoradiotherapy endoscopic response evaluation. Patients achieving a complete response receive 1.5 weeks of consolidation chemoradiotherapy (consolidation gemcitabine and consolidation QD radiation therapy). Patients without a complete response undergo radical cystectomy. Outpatient adjuvant chemotherapy (adjuvant gemcitabine and adjuvant cisplatin) begins 4-5 weeks following the post-consolidation endoscopic evaluation or 8-12 weeks following radical cystectomy, and continues for 12 weeks.
Interventions
15 mg/m\^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.
400mg/m\^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.
27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.
Twice daily (BID) on days 1-5,8-12,15-17. The first daily treatment consists of 1.6 Gy delivered to the pelvis. The second fraction consists of 1.5 Gy to the bladder for the first 5 treatment days. Then, 1.5 Gy is delivered to bladder tumor volume as the second treatment for the remaining 8 treatment days. The bladder tumor volume receives a total of 40.3 Gy.
Once daily (QD) on days (1-5,8-12,15-19,22-26). For the first 10 treatment days, 2 Gy is delivered to the pelvis. Then, 2 Gy is delivered to the bladder for the next 4 treatment days, followed by 2 Gy to the bladder tumor volume for the remaining 6 treatment days. The bladder tumor volume receives a total of 40 Gy.
Twice daily (BID) for 8 days on days 1,2,3,4,5,8,9,10 of consolidation. 1.5 Gy per fraction for a total of 24 Gy delivered to the pelvis.
Once daily (QD) pelvic radiation therapy for 12 days on days 1-5,8-12,15-16 of consolidation. 2 Gy per fraction for a total of 24 Gy delivered to the pelvis.
27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.
400 mg/m\^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.
15 mg/m\^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.
Operable patients who have a pT1 or worse tumor response on re-evaluation following initial transurethral resection and induction chemoradiotherapy will have a radical cystectomy 3-8 weeks following the post-induction response evaluation.
Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.
1000 mg/m\^2 administered intravenously over 30-60 minutes (preferably 30 minutes) on days 1 and 8 of each 21-day cycle for four cycles.
70 mg/m\^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.
Eligibility Criteria
You may qualify if:
- Pathologically (histologically or cytologically) proven diagnosis of primary carcinoma of the bladder (transitional cell cancer) within 8 weeks of registration. Operable patients whose tumors are primary carcinomas of the bladder and exhibit histologic evidence of muscularis propria invasion and are American Joint Committee on Cancer (AJCC) clinical stages T2-T4a, Nx or N0, M0 (Appendix IV) without hydronephrosis; patients who have involvement of the prostatic urethra with transitional cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. T2a, T2b, T3a, T3b -substages‖ are not usually able to be determined with clinical (TURBT) staging.
- If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or percutaneous needle biopsy. Patients with histologically or cytologically confirmed node metastases will not be eligible.
- Patients must have an adequately functioning bladder after thorough evaluation by an urologist and have undergone as thorough a transurethral resection of the bladder tumor as is judged safely possible.
- Patients must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy by the joint agreement of the participating Urologist, Radiation Oncologist, and Medical Oncologist.
- History and physical examination including weight, performance status, and body surface area within 8 weeks prior to study registration
- Zubrod Performance Status ≤ 1
- Age ≥ 18
- Complete blood count (CBC)/differential obtained no more than 4 weeks prior to registration on study, with adequate bone marrow function defined as follows:
- White blood cell count (WBC) ≥ 4000/ml
- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin (hgb) ≥ 10.0 mg/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.);
- Serum creatinine of 1.5 mg% or less; serum bilirubin of 2.0 mg% or less; creatinine clearance of 60 ml/min or greater no more than 4 weeks prior to registration; Note: Calculated creatinine clearance is permissible. If the creatinine clearance is \> 60 ml/min, then a serum creatinine of up to 1.8 mg% is allowable at the discretion of the study chair;
- 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.
- Patient must be able to provide study-specific informed consent prior to study entry.
You may not qualify if:
- Evidence of tumor-related hydronephrosis
- Evidence of distant metastases or histologically or cytologically proven lymph node metastases
- Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy
- 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
- Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease
- Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)
- 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 current Center for Disease Control (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.
- Prior allergic reaction to the study drug(s) involved in this protocol
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Radiation Therapy Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (11)
Georgia Cancer Center for Excellence at Grady Memorial Hospital
Atlanta, Georgia, 30303, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322, United States
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Boise, Idaho, 83706, United States
Cancer Institute at St. John's Hospital
Springfield, Illinois, 62702, United States
Parkview Regional Cancer Center at Parkview Health
Fort Wayne, Indiana, 46805, United States
St. Agnes Hospital Cancer Center
Baltimore, Maryland, 21229, United States
Hudner Oncology Center at Saint Anne's Hospital - Fall River
Fall River, Massachusetts, 02721, United States
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, 48106-0995, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0942, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731, United States
McGill Cancer Centre at McGill University
Montreal, Quebec, H2W 1S6, Canada
Related Publications (1)
Choudhury A, Swindell R, Logue JP, Elliott PA, Livsey JE, Wise M, Symonds P, Wylie JP, Ramani V, Sangar V, Lyons J, Bottomley I, McCaul D, Clarke NW, Kiltie AE, Cowan RA. Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol. 2011 Feb 20;29(6):733-8. doi: 10.1200/JCO.2010.31.5721. Epub 2011 Jan 4.
PMID: 21205754RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Adverse event data was updated when outcome measure 5 was entered.
Results Point of Contact
- Title
- Wendy Seiferheld, M.S.
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
John J. Coen, MD
GenesisCare USA
- STUDY CHAIR
Philip J. Saylor, MD
Massachusetts General Hospital
- STUDY CHAIR
Cheryl T. Lee, MD
University of Michigan Rogel Cancer Center
- STUDY CHAIR
Chin-Lee Wu, MD, PhD
Massachusetts General Hospital
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
October 21, 2008
First Posted
October 22, 2008
Study Start
December 1, 2008
Primary Completion
February 18, 2018
Study Completion
May 20, 2022
Last Updated
June 15, 2022
Results First Posted
August 21, 2019
Record last verified: 2022-05