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

ConditionsLocalized Muscle Invasive Bladder Urothelial Carcinoma Muscle-Invasive Bladder Carcinoma

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorShilpa Gupta, MD

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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)

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

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).
Adaptive Radiotherapy
Radiation
Concurrently, participants will receive an individualized tailored plan for radiation therapy.

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: SG + Adaptive radiotherapyExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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.

Time frame

Within 6 months

Secondary outcomes

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

Determine the bladder intact event-free survival (BI-EFS) with concurrent SG and radiation therapy for MIBC and compare to historical controls with other concurrent chemoradiation regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, radical cystectomy, or death from any cause.

Time frame

Within 2 years

Other outcomes

Novel predictive biomarkers to elucidate determinants of response

Elucidate the molecular and immunologic determinants of response to combined SG and radiotherapy in MIBC to potentially identify novel predictive/PD biomarkers and generate information that may better guide single-agent and combination therapy with antineoplastic drugs. To identify novel biomarkers, biospecimens (ie, blood components, tumor material) will be collected to support analyses of cellular components (eg, protein, DNA, RNA, metabolites) and other circulating molecules.

Time frame

Within 2 years

Correlation between pre-treatment imaging and treatment response

Study the correlation between pre-treatment imaging and response to treatment.

Time frame

Within 2 years

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

Elucidate the genetic and microenvironmental mechanisms that drive efficacy to combined SG plus radiation therapy in bladder cancer via genomic analysis, using whole exome sequencing (WES), RNAseq, and TCRseq

Time frame

Within 2 years

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

Elucidate the genetic and microenvironmental mechanisms that drive resistance to combined SG plus radiation therapy in bladder cancer via genomic analysis, using whole exome sequencing (WES), RNAseq, and TCRseq

Time frame

Within 2 years