SG + Radiation Therapy for Bladder Cancer

Overseen By Shilpa Gupta, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Shilpa Gupta, MD

Must not be taking: Investigational agents

Disqualifiers: Bilateral hydronephrosis, Uncontrolled illness, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should not be receiving other investigational agents or treatments for bladder cancer. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug sacituzumab govitecan for bladder cancer?

Sacituzumab govitecan has shown promising results in treating various cancers, including metastatic urothelial carcinoma and small cell lung cancer, with some patients experiencing tumor shrinkage and improved survival rates. This suggests potential effectiveness for bladder cancer, as it targets Trop-2, a protein often found in these types of cancers. ^{1 2 3 4 5}

Is sacituzumab govitecan safe for humans?

Sacituzumab govitecan has been studied in various cancers and generally shows a safe profile, but some patients experienced side effects like low white blood cell counts (neutropenia), tiredness (fatigue), diarrhea, and low red blood cell counts (anemia). ^{1 2 3 4 6}

What makes the SG + Radiation Therapy treatment for bladder cancer unique?

SG + Radiation Therapy combines sacituzumab govitecan, a drug that targets cancer cells with a specific protein, with adaptive radiotherapy, which adjusts radiation doses based on daily imaging. This approach is novel because it personalizes treatment to the patient's daily condition, potentially improving effectiveness and reducing side effects compared to standard treatments. ^{7 8 9 10 11}

What is the purpose of 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.

Research Team

Shilpa Gupta, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer (MIBC) that's not spread beyond the bladder. They should have had a tumor removal surgery recently and no prior systemic chemotherapy for MIBC. Participants must be in good health otherwise, with normal organ function, and not pregnant or breastfeeding. Those who've received other recent investigational treatments or have certain medical conditions are excluded.

Inclusion Criteria

I haven't had bladder cancer or related types outside the bladder in the last 2 years, except for specific early-stage cancers if I had complete surgery.

Participants must have the ability to understand and the willingness to sign a written informed consent document.

My bladder functions well enough for preservation, with no severe blockages due to the tumor.

Exclusion Criteria

I do not have any uncontrolled illnesses that could interfere with the study.

I have had treatments like chemotherapy or radiation for bladder cancer, but treatments directly into the bladder are okay.

I have issues controlling my bladder, including needing help to urinate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Loading Cycle

Participants receive the first cycle of Sacituzumab Govitecan (SG) 21 days prior to the start of radiation therapy

3 weeks

1 visit (in-person)

Concurrent Treatment

Participants receive two cycles of Sacituzumab Govitecan (SG) with concurrent adaptive radiation therapy

6 weeks

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-5 years

Regular follow-up visits, with phone call communication from years 3-5

Treatment Details

Interventions

• Adaptive Radiotherapy
• Sacituzumab Govitecan

Trial Overview The study tests combining Sacituzumab Govitecan (SG), an IV drug given on specific days of a treatment cycle, with adaptive radiation therapy to see if it's safe and can help preserve the bladder. The trial includes initial SG treatment before starting radiation therapy, followed by two more cycles during radiation.

Participant Groups

Group I: SG + Adaptive radiotherapy Experimental Treatment 2 Interventions

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

Adaptive Radiotherapy 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 (mTNBC)
• Metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer
• Metastatic urothelial cancer (approval being withdrawn)

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Who Is Running the Clinical Trial?

Shilpa Gupta, MD

Lead Sponsor

Trials

1

Recruited

20+

Omar Mian

Lead Sponsor

Trials

2

Recruited

20+

Varian Inc

Collaborator

Trials

1

Recruited

20+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a phase II study involving 113 patients with metastatic urothelial carcinoma who had previously progressed on platinum-based chemotherapy and checkpoint inhibitors, sacituzumab govitecan (SG) demonstrated an objective response rate of 27%, indicating significant efficacy in this difficult-to-treat population.

SG was associated with a manageable safety profile, with the most common severe side effects being neutropenia (35%) and diarrhea (10%), leading to a 6% discontinuation rate due to treatment-related adverse events.

NCBI (Pubmed)

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. Tagawa, ST., Balar, AV., Petrylak, DP., et al.[2022]

Sacituzumab govitecan (SG) is an effective treatment for locally advanced and metastatic urothelial cancer, showing a 27% objective response rate in the TROPHY-U-01 phase II trial.

While SG has common side effects like diarrhea and neutropenia, these can be managed with supportive care, and it has received accelerated approval for patients who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. Mathew Thomas, V., Tripathi, N., Agarwal, N., et al.[2022]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., et al.[2022]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that effectively targets Trop-2, showing significant antitumor effects in various solid tumors, including gastric and pancreatic cancers, in mouse models.

The drug demonstrated a favorable pharmacokinetic profile with a mean residence time of 15.4 hours, and ongoing clinical trials are confirming its anticancer activity in patients with Trop-2 expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Cardillo, TM., Govindan, SV., Sharkey, RM., et al.[2022]

In a study of 171 patients with muscle-invasive bladder cancer, online image-guided adaptive radiation therapy (aRT) with a 7 mm margin showed a significantly higher 5-year freedom from muscle-invasive failure survival rate (98%) compared to conventional radiation therapy (cRT) (75%).

The study found that aRT with a 5 mm margin is not recommended due to lower survival rates and similar toxicity outcomes compared to cRT, indicating that a larger margin may be more effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective review of the long-term outcomes of online adaptive radiation therapy and conventional radiation therapy for muscle invasive bladder cancer. Yeh, J., Bressel, M., Tai, KH., et al.[2022]

In a study of 23 elderly patients with invasive bladder cancer who were unfit for surgery, a modified chemoradiation protocol resulted in a high complete tumor response rate of 89%, demonstrating its efficacy as a treatment option.

The treatment was well-tolerated, with 74% of patients completing the protocol and no treatment-related deaths, suggesting that this approach could be a safe alternative to radical cystectomy for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Chen, WC., Liaw, CC., Chuang, CK., et al.[2019]

A multi-centre feasibility study involving 54 patients with muscle-invasive bladder cancer demonstrated that online adaptive radiotherapy can be effectively implemented across different Radiation Oncology departments.

The study found that a 7mm margin from the clinical target volume (CTV) to planning target volume (PTV) was inadequate, as 18% of patients had the bladder CTV extend beyond the PTV on post-treatment imaging, indicating a need for better bladder filling control or imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcome of a multi-centre feasibility study of online adaptive radiotherapy for muscle-invasive bladder cancer TROG 10.01 BOLART. Foroudi, F., Pham, D., Rolfo, A., et al.[2018]

Daily online adaptive image-guided radiotherapy (RT) for muscle-invasive bladder cancer is feasible and allows for significant sparing of normal tissue compared to conventional RT, with 29% less normal tissue receiving doses over 45 Gy.

Adaptive RT maintained adequate coverage of the clinical target volume (CTV), with only 2.7% of fractions showing inadequate coverage compared to 4.8% for conventional RT, indicating similar efficacy in targeting the tumor while minimizing damage to surrounding healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study. Foroudi, F., Wong, J., Kron, T., et al.[2018]

In a study involving 65 elderly patients with muscle-invasive bladder cancer who were unfit for surgery, a less aggressive chemoradiation protocol using weekly doses of paclitaxel and daily radiation resulted in a 34% overall survival rate at 5 years.

Despite a high incidence of acute treatment-related adverse events (80% in the trastuzumab group and 58% in the paclitaxel-only group), the treatment was generally well tolerated, with few severe complications, allowing many patients to retain their bladders and achieve significant treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation. Dahl, DM., Karrison, TG., Michaelson, MD., et al.[2023]

References

1. 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]

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

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022]

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

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018]

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

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. [2022]

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

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]

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

Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

A retrospective review of the long-term outcomes of online adaptive radiation therapy and conventional radiation therapy for muscle invasive bladder cancer. [2022]

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

Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. [2019]

9. Ireland pubmed.ncbi.nlm.nih.gov

The outcome of a multi-centre feasibility study of online adaptive radiotherapy for muscle-invasive bladder cancer TROG 10.01 BOLART. [2018]

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

Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation. [2023]