Have you or your loved ones been diagnosed with urothelial carcinoma of the bladder?

You may be eligible to participate in a urothelial carcinoma of the bladder clinical trial.

Have you or your loved ones been diagnosed with urothelial carcinoma of the bladder? You may be eligible to participate in a urothelial carcinoma of the bladder clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Urothelial Carcinoma of the Bladder Clinical Trial in Philadelphia PA

NCT02710734 | Phase 2 | Interventional

Have you or your loved ones been diagnosed with urothelial carcinoma of the bladder?

You may be eligible to participate in a urothelial carcinoma of the bladder clinical trial.

Have you or your loved ones been diagnosed with urothelial carcinoma of the bladder? You may be eligible to participate in a urothelial carcinoma of the bladder clinical trial.

Active not recruiting

Male & Female

18 Years +

This study has recruited 78 Participants

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle therapy, chemoradiation or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients.

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Details for the study

Brief Title

Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN)

Official Title

A Phase II Trial of Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN BLADDER)

Brief Summary

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle therapy, chemoradiation or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients.

Detailed Description

This phase II trial studies how well maximal transurethral surgery (surgery performed with a
special instrument inserted through the urethra) followed by accelerated methotrexate,
vinblastine, doxorubicin hydrochloride, cisplatin, and radiation therapy work in treating
patients with bladder cancer that has spread to the muscle. Drugs used in chemotherapy, such
as methotrexate, vinblastine sulfate, doxorubicin hydrochloride, and cisplatin work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy
x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may
kill more tumor cells. Giving combination chemotherapy and radiation therapy before surgery
may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Treatments and/or Procedures

Mitomycin C

Intravenous on day 1 with radiation treatment

Cisplatin

Administered Day 1 of each 14 day cycle for 3 cycles

Doxorubicin

Administered Day 1 of each 14 day cycle for 3 cycles

Vinblastine

Administered Day 1 of each 14 day cycle for 3 cycles

5 FU

Continuous 24hr Intravenous infusion days 1-5 and 16-20 with radiation treatment

Methotrexate

Administered Day 1 of each 14 day cycle for 3 cycles

Transurethral resection of bladder tumor

Performed at before and after AMVAC and after chemoradiation and intravesicle therapy

Intensity modulated radiation therapy IMRT

2.0 Gy per fraction to the whole bladder plus a margin for a total of 32 fractions (64.0 Gy). Radiation will be administered from Monday to Friday

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Other

Quality of life with neoadjuvant AMVAC and subsequent risk-adapted treatment

American Urologic Association (AUA) Symptom Index Score, Sexual Health Inventory for Men (SHIM) score or Female Sexual Function Index (FSFI) score

60 months

Other

Endoscopic Tumor Quantification System score at each TURBT

At each cystoscopic examination, the location and extent of tumor volume will be visually depicted and graded according to Endoscopic Tumor Quantification System

24 months

Study Criteria

Inclusion Criteria:
- Male or female patients ≥18 years.
- Primary urothelial or predominantly urothelial carcinoma of the bladder.
- Histologic evidence of muscularis propria invasion.
- AJCC27 clinical stage T2-T4a .
- No radiographic evidence of lymph node positivity (N0) or metastatic disease (M0).
Clinical lymphadenopathy on staging CT greater than 1.5 cm in short axis must be
biopsy proven negative.
- ECOG performance status 0, 1, or 2.
- Left ventricular ejection fraction ≥ 50% by MUGA or ECHO within 6 months of study
entry.
- Normal organ and bone marrow function as defined:
Leukocytes ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Total
bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 2.5 X
institutional ULN Creatinine Creatinine Clearance ≥ 50 mL/min (calculated using the
Cockroft-Gault formula or measured with 24 hour urine collection)
Exclusion Criteria:
- Any component of small cell histology.
- Prior pelvic radiation therapy or patients who have undergone prior radiation to
greater than or equal to 25% of the bone marrow within the past year are excluded due
to risk of life threatening myelosuppression
- Prior systemic chemotherapy; patients who have received any previous systemic
chemotherapy or radiation therapy for urothelial carcinoma or cytotoxic chemotherapy
for another malignancy within 1 year of study entry are ineligible.
- Prior or concurrent malignancy of any other site except for non-melanoma skin cancer,
unless disease free interval ≥ 5 years.
- Patients who have received experimental agents within 4 weeks of study entry.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Methotrexate, Vinblastine, Adriamycin or Cisplatin or other agents used
in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (defined by current oral or intravenous antibiotic therapy), symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study due to the potential for teratogenic or
abortifacient effects of cytotoxic chemotherapy.
- Known HIV-positive patients on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy.
In addition, these patients are at increased risk of lethal infections when treated
with marrow-suppressive therapy.
- Patients with hydronephrosis that has not been addressed with an intervention such as
placement of a stent.
- Pregnancy & Women of Childbearing Potential