Immunotherapy + Radiation for Bladder Cancer

(RAD-VACCINE Trial)

Overseen By Maryam Anis

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment combining Sasanlimab, which helps the immune system fight cancer, with targeted radiation therapy. It is for patients with muscle-invasive bladder cancer who cannot receive standard chemotherapy. The treatment aims to boost the immune response and directly target cancer cells with radiation.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications like corticosteroids or other immunosuppressive drugs, you may need to stop them 14 days before starting the study treatment.

What data supports the effectiveness of this treatment for bladder cancer?

Research shows that radical cystectomy (surgical removal of the bladder) combined with pelvic lymph node dissection is a standard and effective treatment for muscle-invasive bladder cancer, with studies evaluating long-term outcomes and survival rates in patients. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiation for bladder cancer generally safe for humans?

Research indicates that radical cystectomy and urinary diversion, especially after high-dose pelvic radiation, can have high complication rates. However, a study found that high-dose, short-course preoperative radiation followed by immediate cystectomy did not increase operative morbidity (complications) or mortality (death rates). ^{2 5 6 7 8}

How is the treatment of Immunotherapy + Radiation for Bladder Cancer different from other treatments?

This treatment is unique because it combines immunotherapy, which helps the immune system fight cancer, with radiation therapy, which uses high-energy rays to kill cancer cells, before surgery. This combination aims to enhance the tumor response and potentially improve outcomes for patients with advanced bladder cancer, without increasing side effects. ^{6 7 9 10 11}

Research Team

Raj Satkunasivam, MD

Principal Investigator

Houston Methodist Hospital, Houston Methodist Research Institute

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer who can't have cisplatin chemotherapy. They need good bone marrow and kidney function, no severe infections or heart issues recently, and no history of certain autoimmune diseases or other cancers in the last 2 years. Participants must be willing to use effective contraception.

Inclusion Criteria

More than half of my cancer is urothelial carcinoma.

I can take care of myself and perform daily activities.

I am able to understand and sign the consent form.

Exclusion Criteria

I have an active heart condition.

I have had radiation therapy to my bladder before.

I have had an organ or stem cell transplant.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of sasanlimab followed by 3 doses of stereotactic body radiation therapy

6 weeks

5 visits (in-person)

Surgery

Participants undergo radical cystectomy within 6 weeks of the last dose of sasanlimab

Within 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and quality of life

12 weeks

3 visits (in-person)

Long-term follow-up

Participants are monitored for overall survival and recurrence-free survival

24 months

Treatment Details

Interventions

• Radical Cystectomy + Pelvic Lymph Node Dissection + Urinary Diversion (Surgery)
• Sasanlimab (Checkpoint Inhibitor)
• Stereotactic Body Radiation Therapy (Radiation)

Trial Overview The study tests Sasanlimab (an immune checkpoint inhibitor) combined with stereotactic body radiation therapy before surgery for bladder cancer. It's a phase II trial where all participants receive this combination as a potential 'in-situ vaccine' to boost their immune response against the cancer.

Participant Groups

Group I: Open arm Experimental Treatment 3 Interventions

All patients will receive study interventions (sasanlimab and SBRT) and standard-of-care radical cystectomy.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a study of 125 patients undergoing radical cystectomy for bladder cancer, disease-free survival (DFS) and disease-specific survival (DSS) were significantly influenced by the extent of the tumor, with 100% survival in pT0 tumors and decreasing rates in more advanced stages (pT2: 69.2% DFS, pT4: 39.5% DFS).

Lymph node involvement also impacted survival outcomes, with patients having negative lymph nodes showing a 69.4% DFS compared to 51.8% in those with lymph node metastases, highlighting the importance of timely intervention based on tumor and lymph node status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radical cystectomy in the treatment for bladder carcinoma: results of 125 operated patients]. Babjuk, M., Hanus, T., Safarík, L., et al.[2007]

Patients with a history of pelvic irradiation undergoing radical cystectomy for bladder cancer tend to present with more advanced disease, as indicated by a higher proportion of T4 disease (35% vs 11% in nonirradiated patients).

Despite the more advanced disease, prior pelvic irradiation did not significantly affect bladder cancer recurrence-free survival or specific survival outcomes, suggesting that it is not a predictive factor for survival after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical Cystectomy for Bladder Cancer in Patients With and Without a History of Pelvic Irradiation: Survival Outcomes and Diversion-related Complications. Nguyen, DP., Al Hussein Al Awamlh, B., Faltas, BM., et al.[2015]

In a study of 1,054 patients treated with radical cystectomy for invasive bladder cancer, the 5-year recurrence-free survival rate was 68%, demonstrating the effectiveness of this surgical approach over a median follow-up of 10.2 years.

Patients with organ-confined, lymph node-negative tumors had significantly better outcomes, with 5-year recurrence-free survival rates reaching 92%, while those with lymph node involvement had much lower survival rates of 35%, highlighting the importance of tumor stage and lymph node status in predicting clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. Stein, JP., Lieskovsky, G., Cote, R., et al.[2023]

In a study of 1,054 patients treated with radical cystectomy for invasive bladder cancer, the 5-year recurrence-free survival rate was 68%, demonstrating the effectiveness of this surgical approach over a median follow-up of 10.2 years.

Patients with organ-confined, lymph node-negative tumors had significantly better outcomes, with 5-year recurrence-free survival rates reaching 92%, while those with lymph node involvement had much lower survival rates of 35%, highlighting the importance of tumor stage and lymph node status in predicting clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients. Stein, JP., Lieskovsky, G., Cote, R., et al.[2023]

A national population-based registry in Sweden successfully collected data on 285 out of 435 cystectomies performed in 2011, highlighting the feasibility of tracking complications and outcomes in bladder cancer surgeries.

The study found that longer operating times (over 318 minutes) and older age (76-89 years) were significantly associated with an increased risk of complications, with 36% of patients experiencing complications post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database. Jerlström, T., Gårdmark, T., Carringer, M., et al.[2022]

In a study of 148 patients who underwent radical cystectomy after receiving high-dose pelvic radiation, the early complication rate was found to be higher than in non-irradiated patients, with 335 complications reported within 90 days post-surgery.

Factors such as being over 65 years old and having a higher American Society of Anesthesiologists score were significant predictors of postoperative complications, while the type of urinary diversion did not significantly impact complication rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early complications of cystectomy after high dose pelvic radiation. Eisenberg, MS., Dorin, RP., Bartsch, G., et al.[2010]

High dose, short course preoperative radiation therapy (1,660 rad over 4 days) followed by immediate cystectomy for bladder cancer does not increase the risk of operative morbidity or mortality, making it a safe approach.

The study found that the incidence of nodal involvement in bladder cancer patients varied significantly, highlighting the importance of pelvic node treatment during cystectomy, especially for more advanced tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with high dose, short course preoperative radiation therapy and immediate single stage cystectomy in management of bladder cancer: a preliminary report. Skinner, DG., Kaufman, JJ., Tift, JP.[2006]

In a study of 196 patients who underwent robot-assisted radical cystectomy (RARC) for bladder cancer, 80% experienced some form of complication within 90 days post-surgery, highlighting the significant morbidity associated with this procedure.

Major complications occurred in 35% of patients, with the most common issues being infections and gastrointestinal problems, indicating that while RARC is a minimally invasive option, it still carries substantial risks that need careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardized analysis of frequency and severity of complications after robot-assisted radical cystectomy. Yuh, BE., Nazmy, M., Ruel, NH., et al.[2022]

Immunotherapy is becoming increasingly important in treating kidney and bladder cancers, showing promise in improving patient outcomes.

Combining immunotherapy with radiotherapy may enhance tumor response, including in cases of metastatic tumors, based on encouraging preclinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination radiotherapy-immunotherapy in genitourinary cancer]. Ollivier, L., Guimas, V., Rio, E., et al.[2021]

The RACE IT trial is investigating the safety and feasibility of combining the PD-1 inhibitor Nivolumab with radiation therapy in patients with locally advanced bladder cancer, aiming to improve treatment outcomes for those ineligible for standard chemotherapy.

The study will involve 33 patients receiving Nivolumab and radiation before undergoing radical cystectomy, with the primary goal of assessing the completion rate of this combined treatment by week 15.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT). Schmid, SC., Koll, FJ., Rödel, C., et al.[2020]

In a study of five patients with node-positive bladder cancer, radical treatment including pelvic radiotherapy was well-tolerated, with only minimal gastrointestinal and urinary symptoms reported, indicating a favorable safety profile.

Local control of the disease was effective, as none of the patients experienced pelvic relapse, although two did develop distant metastatic disease, suggesting that while the treatment is promising, further research is needed to identify which patients would benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The delivery of radical radiotherapy to the bladder and pelvis in node-positive (N1) bladder cancer: a five patient case series. Fackrell, DG., Ford, D., Chetiyawardana, S., et al.[2022]

References

1. Czech Republic pubmed.ncbi.nlm.nih.gov

[Radical cystectomy in the treatment for bladder carcinoma: results of 125 operated patients]. [2007]

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

Radical Cystectomy for Bladder Cancer in Patients With and Without a History of Pelvic Irradiation: Survival Outcomes and Diversion-related Complications. [2015]

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

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. [2023]

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

Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients. [2023]

5. Sweden pubmed.ncbi.nlm.nih.gov

Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database. [2022]

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

Early complications of cystectomy after high dose pelvic radiation. [2010]

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

Experience with high dose, short course preoperative radiation therapy and immediate single stage cystectomy in management of bladder cancer: a preliminary report. [2006]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Standardized analysis of frequency and severity of complications after robot-assisted radical cystectomy. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Combination radiotherapy-immunotherapy in genitourinary cancer]. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT). [2020]

11. England pubmed.ncbi.nlm.nih.gov

The delivery of radical radiotherapy to the bladder and pelvis in node-positive (N1) bladder cancer: a five patient case series. [2022]