Pre-Surgery Sacituzumab Govitecan for Bladder Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Petros Grivas

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Washington

Must not be taking: Irinotecan, Topotecan

Disqualifiers: Neuroendocrine histology, Active infection, Hepatitis, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether sacituzumab govitecan given before radical cystectomy works in treating patients with non-urothelial bladder cancer. Sacituzumab govitecan contains a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan before radical cystectomy may make the surgery more effective in patients with muscle invasive bladder cancer.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does exclude those who have had prior systemic anti-cancer therapy within 4 weeks or prior radiation therapy within 2 weeks, and those on medications that interfere with certain enzymes. It's best to discuss your specific medications with the trial team.

Is sacituzumab govitecan generally safe for humans?

Sacituzumab govitecan has been used for treating breast and urothelial cancers, but it can cause side effects like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). Most side effects occur within 30 days of starting treatment, and some may lead to hospitalization, especially in males. ^{1 2 3 4 5}

How is the drug sacituzumab govitecan unique for bladder cancer treatment?

Sacituzumab govitecan is unique because it is an antibody-drug conjugate that targets Trop-2, a protein often found in high amounts on cancer cells, and delivers SN-38, a powerful cancer-fighting agent, directly to these cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{1 2 4 5 6}

Research Team

Petros Grivas

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults with muscle invasive bladder cancer who haven't had major surgery or other cancer treatments recently. They must be fit enough for radical cystectomy, not pregnant or breastfeeding, and willing to use contraception. People with neuroendocrine/small cell histology, another interfering malignancy, significant heart disease, active infections requiring antibiotics, or known allergies to the study drug are excluded.

Inclusion Criteria

Your body has enough infection-fighting cells.

I am not suitable for cisplatin treatment or I have refused it after being advised.

Your bilirubin levels must be within a certain range.

Exclusion Criteria

I do not have another cancer that could affect the study's results.

I have an active hepatitis B or C infection.

I am currently on antibiotics for an infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan intravenously over 3 hours on days 1 and 8 of each cycle. Treatment repeats every 21 days for 3 cycles.

9 weeks

6 visits (in-person)

Surgery

Participants undergo radical cystectomy and pelvic lymph node dissection within 2-6 weeks after the last dose of treatment.

2-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at 1-3 months after surgery and then every 3-6 months for 2 years.

2 years

Treatment Details

Interventions

• Sacituzumab Govitecan (Monoclonal Antibodies)

Trial Overview The trial is testing Sacituzumab Govitecan given before surgery (radical cystectomy) in patients with non-urothelial bladder cancer. It's a phase II study to see if this targeted therapy that delivers chemotherapy directly to cancer cells can improve surgical outcomes.

Participant Groups

Group I: Treatment (sacituzumab govitecan) Experimental Treatment 3 Interventions

Patients receive sacituzumab govitecan IV over 3 hours on days 1 and 8 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks after last dose, patients undergo radical cystectomy and pelvic lymph node dissection.

Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

🇪🇺 Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

🇨🇦 Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Fred Hutch/University of Washington Cancer Consortium Seattle, WA

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1858

Patients Recruited

2,023,000+

Gilead Sciences

Industry Sponsor

Trials

1150

Patients Recruited

878,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022] Despite rapid advances in the treatment landscape of urothelial cancer, there is a substantial unmet need for safe and effective therapies for patients with locally advanced and metastatic urothelial cancer. Sacituzumab govitecan (SG) is an antibody-drug conjugate, consisting of a Trop-2 directed monoclonal antibody linked to SN-38, the active metabolite of irinotecan. Trop-2 is a glycoprotein overexpressed in various carcinomas, including urothelial carcinomas.

2. England pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. [2023] The antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018).

3. United States pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023] Sacituzumab govitecan(SG)is wide used for the treatment of breast cancer and urothelial carcinoma, but available information regarding AEs is limited. We aim to explore the AE induced by SG by mining the FAERS database.The association between SG and adverse events (AEs) were evaluated using the information component (IC). A multivariate logistic regression analysis was conducted for all identified signals to explore the risk factors associated with AEs leading to hospitalization.In total1884 reports related to SG were retrieved, and 114 AE signals involving 20 systems were identified. The median time for onset of AEs was around 6-7 days after initiating treatment with SG, with over 80% of AEs occurring within 30 days. Subgroup analysis revealed that 14 signals were reported in the males and 110 in the females. There were 58 signals reported in patients under 65 following the use of SG, 59 signals in patients over 65, and 31 signals were present in both groups. Multivariable analysis showed that the males and the occurrence of Colitis, Pneumonitis, Febrile Neutropenia, Pyrexia, Sepsis, Dehydration, and Diarrhea were risk factors leading to hospitalization with an AUC of 0.89. Additionally, sensitivity analysis revealed that this study had good robustness.This is the first retrospective analysis based on FAERS to review the safety of SG. The results highlight the need to closely monitor adverse reactions such as neutropenia, diarrhea, colitis, and sepsis when using SG.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021] Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.

5. United States pubmed.ncbi.nlm.nih.gov

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. [2022] Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

6. England pubmed.ncbi.nlm.nih.gov

The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer. [2022] The treatment landscape of advanced bladder cancer continues to evolve with novel therapeutics approved in recent years and many in the pipeline. Here we review the role of the novel agents enfortumab vedotin and sacituzumab govitecan in treatment of advanced disease.