SG + Radiation Therapy for Bladder Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Omar Mian, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Shilpa Gupta, MD

Must not be taking: Investigational agents

Disqualifiers: Bilateral hydronephrosis, Uncontrolled illness, Pregnancy, others

No Placebo Group

Trial Summary

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.

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.

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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).

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, OH

Who Is Running the Clinical Trial?

Shilpa Gupta, MD Lead Sponsor

Omar Mian Lead Sponsor

Varian Inc Collaborator

Gilead Sciences Industry Sponsor

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] 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.

2. 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.

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] Sacituzumab govitecan (IMMU-132), an antitrophoblastic cell-surface antigen (anti-Trop-2) humanized antibody-SN-38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU-132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers.

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] Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.

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] Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.

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] Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) made from a humanized anti-Trop-2 monoclonal antibody (hRS7) conjugated with the active metabolite of irinotecan, SN-38. In addition to its further characterization, as the clinical utility of IMMU-132 expands to an ever-widening range of Trop-2-expressing solid tumor types, its efficacy in new disease models needs to be explored in a nonclinical setting. Unlike most ADCs that use ultratoxic drugs and stable linkers, IMMU-132 uses a moderately toxic drug with a moderately stable carbonate bond between SN-38 and the linker. Flow cytometry and immunohistochemistry disclosed that Trop-2 is expressed in a wide range of tumor types, including gastric, pancreatic, triple-negative breast (TNBC), colonic, prostate, and lung. While cell-binding experiments reveal no significant differences between IMMU-132 and parental hRS7 antibody, surface plasmon resonance analysis using a Trop-2 CM5 chip shows a significant binding advantage for IMMU-132 over hRS7. The conjugate retained binding to the neonatal receptor, but it lost greater than 60% of the antibody-dependent cell-mediated cytotoxicity activity compared to that of hRS7. Exposure of tumor cells to either free SN-38 or IMMU-132 demonstrated the same signaling pathways, with pJNK1/2 and p21(WAF1/Cip1) upregulation followed by cleavage of caspases 9, 7, and 3, ultimately leading to poly-ADP-ribose polymerase cleavage and double-stranded DNA breaks. Pharmacokinetics of the intact ADC in mice reveals a mean residence time (MRT) of 15.4 h, while the carrier hRS7 antibody cleared at a similar rate as that of the unconjugated antibody (MRT ∼ 300 h). IMMU-132 treatment of mice bearing human gastric cancer xenografts (17.5 mg/kg; twice weekly × 4 weeks) resulted in significant antitumor effects compared to that of mice treated with a nonspecific control. Clinically relevant dosing schemes of IMMU-132 administered either every other week, weekly, or twice weekly in mice bearing human pancreatic or gastric cancer xenografts demonstrate similar, significant antitumor effects in both models. Current Phase I/II clinical trials ( ClinicalTrials.gov , NCT01631552) confirm anticancer activity of IMMU-132 in cancers expressing Trop-2, including gastric and pancreatic cancer patients.

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] To report long-term outcomes of online image-guided (IG) adaptive radiation therapy (aRT) versus conventional IG radiation therapy (cRT) for bladder preservation in muscle-invasive bladder cancer (MIBC).

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

Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. [2019] To investigate the tolerance and efficacy of a modified concurrent chemoradiation (CCRT) protocol for patients with invasive bladder cancer "unfit" for radical cystectomy.

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] To assess whether online adaptive radiotherapy for bladder cancer is feasible across multiple Radiation Oncology departments using different imaging, delivery and recording technology.

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

Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study. [2018] To determine the advantages and disadvantages of daily online adaptive image-guided radiotherapy (RT) compared with conventional RT for muscle-invasive bladder cancer.

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] Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered.