Adaptive RADiation Therapy With Concurrent Sacituzumab Govitecan (SG) for Muscle Invasive Bladder Cancer

NCT05833867 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE9822
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the safety and tolerability of treatment with concurrent Sacituzumab Govitecan (SG) and adaptive radiation therapy. The main objective is to establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for participants with localized MIBC. Participants will receive the study drug, SG, through an IV once weekly on days 1 and 8 of each 21-day treatment cycle. The first cycle of SG will begin 21 days prior to the scheduled start of radiation therapy. The second and third cycles of SG will be given while the participant is receiving radiation therapy. Participants will be asked to undergo computed tomography (CT) and magnetic resonance imaging (MRI) pre-and post-treatment. Participation in the research will last up to 5 years, depending on treatment outcomes, with a treatment period of 8 weeks and a study follow-up period of up to 2-5 years thereafter, and a survival follow-up, with only phone call communication from years 3-5.

Conditions

Localized Muscle Invasive Bladder Urothelial Carcinoma; Muscle-Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of acute-dose limiting toxicities

  To establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. This will be assessed by estimating the rate of acute dose-limiting toxicities occurring during Cycles 2-3 of treatment.

  Within 6 months

Secondary Outcomes (1)

• Determine the bladder intact event-free survival (BI-EFS)

  Within 2 years

Other Outcomes (7)

• Novel predictive biomarkers to elucidate determinants of response

  Within 2 years

• Correlation between pre-treatment imaging and treatment response

  Within 2 years

• Identify the genetic and microenvironmental mechanisms that drive efficacy to combined SG plus radiation therapy in bladder cancer

  Within 2 years

Study Arms (1)

SG + Adaptive radiotherapy

EXPERIMENTAL

Sacituzumab Govitecan, IV, 8 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy

Drug: Sacituzumab govitecan; Radiation: Adaptive Radiotherapy

Interventions

Sacituzumab govitecan DRUG

8 mg/kg Sacituzumab Govitecan is to be administered intravenously in 21-day cycles on Day 1 and Day 8; the next cycle should start a minimum of 14 days after the Day 8 dose (i.e., the Day 8 infusion will be counted as the first day of that 14-day period).

Also known as: TRODELVY

SG + Adaptive radiotherapy

Adaptive Radiotherapy RADIATION

Concurrently, participants will receive an individualized tailored plan for radiation therapy.

SG + Adaptive radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed muscle-invasive bladder cancer (MIBC) (T2-T4aN0M0). Participants with mixed urothelial carcinoma will be eligible for the trial, except for small cell or neuroendocrine component
• Participants must have received no prior systemic chemotherapy for this disease. Participants must refuse conventional radio-sensitizing chemotherapy, (and/or) must not be eligible for or refuse cystectomy while on study Participants may receive cystectomy following the end of treatment (EOT)/ Safety Visit if deemed necessary by their clinical team while still in follow-up.
• Performance status: ECOG Performance status ≤ 2
• Participants must have normal organ and marrow function as defined below:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x laboratory upper limit of normal (ULN)
• Total serum bilirubin ≤ 2.0 x ULN
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin ≥ 9.0 g/dL
• Serum calcium ≤ 12.0 mg/dL
• Calculated Creatinine Clearance ≥ 30 mL/min. Calculated using Cockcroft-Gault formula: Creatinine Clearance = \[\[140 - age(yr)\] multiplied by body weight(kg)\]/ \[72 multiplied by serum Cr(mg/dL)\] (multiply total by 0.85 for women).
• Participants must have adequate baseline bladder function to warrant bladder preservation as assessed by the treating provider, including absence of bilateral hydronephrosis or acute obstruction related to bladder tumor after TURBT. Unilateral hydronephrosis is permitted.
• Participants must undergo a TURBT within ≤ 60 days prior to treatment start. In a situation where a participant is referred from an outside site to the Cleveland Clinic Foundation, participant must have a repeat cystoscopy by the urologist who will be following the participant on the clinical trial to assess the adequacy of the prior TURBT. Participant may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist.
• Participants may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection.
• Participant must undergo radiological staging within 60 days prior to treatment start. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Participants must not have evidence of T4b and/or N1-3 dT4bN1-3 disease. Eligibility is based on review by Cleveland Clinic Foundation (CCF) radiology department and/or PI.

You may not qualify if:

• Participants receiving or utilizing any other investigational agents or devices.
• Has received prior pelvic / local radiation therapy for MIBC or any other cancer type.
• Has received any prior systemic treatment, chemoradiation, and / or radiation therapy for MIBC or non-muscle-invasive bladder cancer (NMIBC). Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted.
• Has diagnosed Bilateral hydronephrosis.
• Has limited bladder function as noted by a provider, with frequency of small amounts of urine, urinary incontinence including stress/urge, requires self-catheterization or a permanent indwelling catheter.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SG or any of its' components.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because SG and radiation effects during pregnancy have potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with SG, breastfeeding should be discontinued if the mother is treated with Sacituzumab Govitecan.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Note: Participants who have entered the Follow-up Phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Shilpa Gupta, MD: lead
• Varian Inc: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Interventions

sacituzumab govitecan

Study Officials

• Shilpa Gupta, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shilpa Gupta, MD

CONTACT

1-866-223 8100; TaussigResearch@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 27, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: During the course of the study and indefinitely thereafter as a peer reviewed publication
• Access Criteria: All data shared with parties will be done once all PHI is redacted if applicable, and only under the fulled execution of the appropriate confidentiality agreements set up by the CCF legal team

Locations

US (1)