- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02710734
Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN)
December 7, 2023 updated by: Fox Chase Cancer Center
A Phase II Trial of Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN BLADDER)
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.
Study Overview
Status
Active, not recruiting
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
78
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
District of Columbia
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Washington, District of Columbia, United States, 20010
- Washington Cancer Institute at MedStar Washington Hospital Center
-
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, United States, 19107
- Sidney Kimmel Cancer Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CRT
Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3
|
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
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
Performed at before and after AMVAC and after chemoradiation and intravesicle therapy
Continuous 24hr Intravenous infusion days 1-5 and 16-20 with radiation treatment
Intravenous on day 1 with radiation treatment
|
Experimental: Surveillance
Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance
|
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Performed at before and after AMVAC and after chemoradiation and intravesicle therapy
|
Experimental: Intravesicle therapy
Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3
|
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Performed at before and after AMVAC and after chemoradiation and intravesicle therapy
|
Experimental: Radical Cystectomy
Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy
|
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Administered Day 1 of each 14 day cycle for 3 cycles
Performed at before and after AMVAC and after chemoradiation and intravesicle therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Metastasis-free survival (MFS) at 2 years.
Time Frame: 24 months
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Ability to complete of 3 cycles of neoadjuvant AMVAC and chemoradiation therapy with 5-FU and mitomycin C.
Time Frame: Up to 37 Weeks
|
Up to 37 Weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of urothelial carcinoma recurrence in active surveillance patients
Time Frame: 60 months
|
60 months
|
|
Overall survival and PFS of the entire cohort
Time Frame: 60 months
|
60 months
|
|
toxicity during each treatment arm according to NCI CTCAE v 4.01 criteria
Time Frame: 24 months
|
24 months
|
|
Proportion of patients with ≥cT1 disease after TURBT#2
Time Frame: up to 22 weeks
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up to 22 weeks
|
|
Proportion of patients requiring a cystectomy, either immediately after TURBT#2 or as salvage after surveillance or CRT
Time Frame: up to 24 months
|
up to 24 months
|
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Endoscopic Tumor Quantification System score at each TURBT
Time Frame: 24 months
|
At each cystoscopic examination, the location and extent of tumor volume will be visually depicted and graded according to Endoscopic Tumor Quantification System
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24 months
|
Quality of life with neoadjuvant AMVAC and subsequent risk-adapted treatment
Time Frame: 60 months
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American Urologic Association (AUA) Symptom Index Score, Sexual Health Inventory for Men (SHIM) score or Female Sexual Function Index (FSFI) score
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60 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 24, 2016
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
February 1, 2034
Study Registration Dates
First Submitted
February 18, 2016
First Submitted That Met QC Criteria
March 11, 2016
First Posted (Estimated)
March 17, 2016
Study Record Updates
Last Update Posted (Estimated)
December 11, 2023
Last Update Submitted That Met QC Criteria
December 7, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Urinary Bladder Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Doxorubicin
- Methotrexate
- Mitomycins
- Mitomycin
- Vinblastine
Other Study ID Numbers
- GU-086
- 15-1071 (Other Identifier: Fox Chase Cancer Center IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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