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

NCT ID: NCT02710734

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-24

Study Completion Date

2034-02-28

Brief Summary

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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

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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.

Conditions

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Urothelial Carcinoma of the Bladder

Keywords

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Urothelial

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CRT

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Vinblastine

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Doxorubicin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Cisplatin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Intensity modulated radiation therapy (IMRT)

Intervention Type RADIATION

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

Transurethral Resection of Bladder tumor

Intervention Type PROCEDURE

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

5-FU

Intervention Type DRUG

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

Mitomycin C

Intervention Type DRUG

Intravenous on day 1 with radiation treatment

Surveillance

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Vinblastine

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Doxorubicin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Cisplatin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Transurethral Resection of Bladder tumor

Intervention Type PROCEDURE

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

Intravesicle therapy

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Vinblastine

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Doxorubicin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Cisplatin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Transurethral Resection of Bladder tumor

Intervention Type PROCEDURE

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

Radical Cystectomy

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Vinblastine

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Doxorubicin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Cisplatin

Intervention Type DRUG

Administered Day 1 of each 14 day cycle for 3 cycles

Transurethral Resection of Bladder tumor

Intervention Type PROCEDURE

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

Interventions

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Methotrexate

Administered Day 1 of each 14 day cycle for 3 cycles

Intervention Type DRUG

Vinblastine

Administered Day 1 of each 14 day cycle for 3 cycles

Intervention Type DRUG

Doxorubicin

Administered Day 1 of each 14 day cycle for 3 cycles

Intervention Type DRUG

Cisplatin

Administered Day 1 of each 14 day cycle for 3 cycles

Intervention Type DRUG

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

Intervention Type RADIATION

Transurethral Resection of Bladder tumor

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

Intervention Type PROCEDURE

5-FU

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

Intervention Type DRUG

Mitomycin C

Intravenous on day 1 with radiation treatment

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fox Chase Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Washington Cancer Institute at MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Johns Hopkins

Baltimore, Maryland, United States

Site Status

Sidney kimmel Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Geynisman DM, Abbosh PH, Ross E, Zibelman MR, Ghatalia P, Anari F, Mark JR, Stamatakis L, Hoffman-Censits JH, Viterbo R, Greenberg RE, Churilla TM, Horwitz EM, Hallman MA, Smaldone MC, Uzzo R, Chen DYT, Kutikov A, Plimack ER. Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1). J Clin Oncol. 2025 Mar 20;43(9):1113-1122. doi: 10.1200/JCO-24-01214. Epub 2024 Dec 16.

Reference Type DERIVED
PMID: 39680823 (View on PubMed)

Jiang DM, Chung P, Kulkarni GS, James ND, Sridhar SS. Lack of Evidence Does Not Equal Lack of Benefit: Neoadjuvant Chemotherapy and Trimodality Therapy in Selected Patients with Muscle-Invasive Bladder Cancer : In response to: Dirk Bohmer and Arne Grun. Lacking Evidence to Recommend Neoadjuvant Chemotherapy and Definitive Radiotherapy in Muscle-Invasive Bladder Cancer. Curr Oncol Rep. 2021 Mar 3;23(3):36. doi: 10.1007/s11912-021-01035-9. No abstract available.

Reference Type DERIVED
PMID: 33660142 (View on PubMed)

Other Identifiers

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15-1071

Identifier Type: OTHER

Identifier Source: secondary_id

GU-086

Identifier Type: -

Identifier Source: org_study_id