Clinical trial NCT02716896: Radical Cystectomy Compared With Chemoradiation for Muscle Invasive Bladder Cancer
Official title: Radical Cystectomy Compared With Chemoradiation for Muscle Invasive Bladder Cancer: A Pilot, Randomized-Controlled Non-Inferiority Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Muscle Invasive Bladder Cancer
Keywords: cystectomy
radiation
chemotherapy
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2016-03-23
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Currently the standard treatment of muscle invasive bladder cancer is the complete removal of bladder and adjacent organs, such as prostate or ovaries. Radical cystectomy is fraught with complications and risk of death. The researchers hope to learn if chemoradiation (i.e. using chemotherapy and radiation), also an acceptable treatment for muscle invasive bladder cancer, can be used a good alternative therapy option.

Detailed description: Currently the standard treatment of muscle invasive bladder cancer is the complete removal of bladder and adjacent organs, such as prostate or ovaries. Such procedure is highly invasive and undesirable for some patients.

The researchers hope to learn if chemoradiation, using chemotherapy and radiation, can be a good alternative therapy option. Chemoradiation therapy is also currently considered an acceptable clinical approach but is typically used for treatment in patients with muscle invasive bladder cancer who have other medical issues that might cause complications during or after undergoing surgery. Disease free survival at 5 years is better for those who had their bladder removed, but overall survival rates for chemoradiation therapy patients are comparable between the two approaches.

Eligibility criteria: Inclusion Criteria:

* Pathologically (histologically) 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 AJCC clinical stages T2-T4a, Nx or N0, M0
* 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 or any other 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 0-2
* Age ≥ 18;
* CBC (Complete blood count)/differential obtained no more than 4 weeks prior to registration on study, with adequate bone marrow function defined as follows:

  1. WBC (white bloodcell count) ≥ 4000/ml
  2. Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
  3. Platelets ≥ 100,000 cells/mm3;
  4. Hemoglobin ≥ 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 principle investigator;
* 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

Exclusion Criteria:

* Unable and unwilling to provide informed consent
* 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 (plasma nitrate)+ 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 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.
* Is pregnant; women of childbearing potential and male participants unwilling to practice adequate contraception.

Primary outcomes:
measure: Total Number of Participants Adhere to the Assigned Treatment
timeFrame: One year
measure: Total Number of Participants Withdraw From the Study
timeFrame: One year
measure: Total Number of Participants Completed the Study
timeFrame: One year
Secondary outcomes:
measure: Change From Baseline and Year 1 in Health Related Quality of Life Measures
timeFrame: One year
measure: Total Number of Participants Who Are Able to Keep Their Bladder Within the Time Frame of the Study
timeFrame: One year
measure: Total Number of Participants Who Remained Progression-free Within the Time Frame of the Study
timeFrame: One year
measure: Change From Baseline Level to Year 1 on Genomic Markers After Chemoradiation
timeFrame: One year
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
References: