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Bladder CancerPhase 2NCT00777491

Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery

A Phase 2 study testing induction cisplatin, induction 5-fluorouracil and induction gemcitabine in people with Bladder Cancer, run by Radiation Therapy Oncology Group at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Bladder Cancer
What is being tested?
induction cisplatin, induction 5-fluorouracil and induction gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
11 sitesin 2 countries
Study dates
Dec 2008to 20 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • 8.1 White blood cell count (WBC) ≥ 4000/ml
  • 8.2 Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
  • 8.3 Platelets ≥ 100,000 cells/mm3;
  • 8.4 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.

Who cannot join

  • 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)
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  • Severe, active co-morbidity, defined as follows:
  • 7.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  • 7.2 Transmural myocardial infarction within the last 6 months;
  • 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
  • 7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
  • 7.5 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.
  • 7.6 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.
  • 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.
  • Prior allergic reaction to the study drug(s) involved in this protocol

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States10 sites

  • Saint Joseph Mercy Cancer Center

    Ann Arbor, Michigan, 48106-0995

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0942

  • Georgia Cancer Center for Excellence at Grady Memorial Hospital

    Atlanta, Georgia, 30303

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • St. Agnes Hospital Cancer Center

    Baltimore, Maryland, 21229

  • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

    Boise, Idaho, 83706

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

    Fall River, Massachusetts, 02721

  • Parkview Regional Cancer Center at Parkview Health

    Fort Wayne, Indiana, 46805

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • Cancer Institute at St. John's Hospital

    Springfield, Illinois, 62702

Other trials in United States

Canada1 site

  • McGill Cancer Centre at McGill University

    Montreal, Quebec, H2W 1S6

Other trials in Canada

About this study

Official title: 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

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.

Read the detailed description

OBJECTIVES:

Primary

  • To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin.

Secondary

  • To estimate the treatment completion rate in these patients.
  • To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients.
  • To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients.
  • To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients.
  • To estimate the value of tumor histopathologic, molecular genetic, DNA content, metabolomic, and proteomic parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival.
  • To analyze for American Urological Association (AUA) Symptom scores at baseline and at 3 years from patients on both arms.
  • To find potentially predictive biomarkers for cystectomy-free survival.
  • To find potentially predictive biomarkers for acute and late toxicities.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.

Conditions
Bladder Cancer
Being tested
induction cisplatin, induction 5-fluorouracil, induction gemcitabine, Induction BID radiation therapy, Induction QD radiation therapy
Keywords
stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • induction cisplatinDrug

    15 mg/m^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.

  • induction 5-fluorouracilDrug

    Also called fluorouracil, 5-FU

    400mg/m^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.

  • induction gemcitabineDrug

    Also called gemcitabine hydrochloride

    27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.

  • Induction BID radiation therapyRadiation

    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.

  • Induction QD radiation therapyRadiation

    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.

  • Consolidation BID radiation therapyRadiation

    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.

  • Consolidation QD radiation therapyRadiation

    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.

  • consolidation gemcitabineDrug

    Also called gemcitabine hydrochloride

    27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.

  • consolidation 5-fluorouracilDrug

    Also called fluorouracil, 5-FU

    400 mg/m^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.

  • consolidation cisplatinDrug

    Also called cisplatin

    15 mg/m^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.

  • radical cystectomyProcedure or surgery

    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.

  • Post-Induction Chemoradiotherapy Endoscopic Response EvaluationProcedure or surgery

    Also called TUR

    Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.

  • adjuvant gemcitabineDrug

    Also called gemcitabine hydrochloride

    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.

  • adjuvant cisplatinDrug

    70 mg/m^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.

Study groups in NCT00777491
Study groupRoleWhat they receive
5-FU and Cisplatin + BID IrradiationExperimentalWithin 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.
Receives: Drug: induction cisplatin; Drug: induction 5-fluorouracil; Radiation: Induction BID radiation therapy; Radiation: Consolidation BID radiation therapy; Drug: consolidation 5-fluorouracil; Drug: consolidation cisplatin; Procedure: radical cystectomy; Procedure: Post-Induction Chemoradiotherapy Endoscopic Response Evaluation; Drug: adjuvant gemcitabine; Drug: adjuvant cisplatin
Gemcitabine + QD IrradiationExperimentalWithin 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.
Receives: Drug: induction gemcitabine; Radiation: Induction QD radiation therapy; Radiation: Consolidation QD radiation therapy; Drug: consolidation gemcitabine; Procedure: radical cystectomy; Procedure: Post-Induction Chemoradiotherapy Endoscopic Response Evaluation; Drug: adjuvant gemcitabine; Drug: adjuvant cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From randomization to three years

Secondary outcomes (7)

  1. Percentage of Patients Who Completed Treatment Per Protocol

    Treatment administration data was centrally reviewed to determine if patients completed each treatment component per protocol.

    Measured: After each treatment component (induction, consolidation, adjuvant). Timing varies bases on arm, tumor response at multiple time points, and allowed time ranges.

  2. Percentage of Patients With Grade 3 or Higher Genitourinary, Gastrointestinal, or Hematologic Adverse Events

    Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. All adverse events are counted, regardless of reported relationship to protocol treatment.

    Measured: 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.

  3. Number of Patients Experiencing Complete Response of the Primary Tumor After Induction Therapy

    Patients will be considered as having a clinical complete response when all biopsies are negative at the site(s) of the pretreatment tumor(s).

    Measured: 3-4 weeks following induction therapy (approximately maximum 8 weeks from start of treatment depending on treatment arm and allowed time windows)

  4. Number of Participants With Progression or Removal of Bladder Five Years After Therapy

    Progression is defined as an increase of 50% or more in the largest diameter of the endoscopically appreciable tumor in the tumor-site biopsy specimen, the development of new bladder tumors, or the development of metastatic disease.

    Measured: 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.

  5. Change in American Urological Association Symptom Index (AUASI) Score at 3 Years

    The AUASI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as 3-year score - baseline score such that a negative change indicates improvement.

    Measured: Baseline and 3 years

  6. Determining Potentially Predictive Biomarkers for Acute and Late Toxicities

    Measured: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out

  7. Determining Potentially Predictive Biomarkers for Cystectomy-free Survival

    Measured: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this out

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2008 (estimated)
  2. Study startDec 2008
  3. Primary completion18 Feb 2018
  4. Study completion20 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00777491
Sponsor's protocol ID
RTOG-0712
Other IDs
CDR0000616858
Status last verified
May 2022
First submitted
21 Oct 2008
Last updated
15 Jun 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21205754

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing induction cisplatin, induction 5-fluorouracil and induction gemcitabine in people with Bladder Cancer, run by Radiation Therapy Oncology Group at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Patients Without Distant Metastases by Three Years (time frame: From randomization to three years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00777491, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.

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