ACTIVE_NOT_RECRUITING

Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

Conditions

Urothelial Carcinoma Bladder Bladder Cancer Muscle Invasive Bladder Cancer Immune Checkpoint Inhibitor Immunotherapy Urothelial Carcinoma of the Bladder Urologic neoplasms Neoadjuvant therapy Radiation Stereotactic Body Radiation Therapy Urinary Bladder Diseases Urologic Diseases Sasanlimab Antineoplastic agents Antineoplastic agents, Immunological

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a prospective, single-institution, single-arm, phase II clinical trial that tests a novel strategy of neoadjuvant Sasanlimab, an immune checkpoint inhibitor (ICI), in combination with stereotactic body radiation therapy as an in-situ vaccination in patients, who are ineligible to receive cisplatin-based chemotherapy and undergoing radical cystectomy for muscle-invasive bladder cancer.

Official Title

A Phase II Clinical Trial of Neoadjuvant Sasanlimab and Stereotactic Body Radiation Therapy as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

Quick Facts

Study Start:2022-02-15

Study Completion:2027-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05241340

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Capable of giving signed informed consent 2. Age ≥ 18 years 3. ECOG Eastern Cooperative Oncology Group performance status 0-2 4. Predominant (\>50%) urothelial carcinoma histology 5. Muscle-invasive bladder cancer (cT2-4a, cN0, cM0) 6. Decline/refuse OR Ineligible to receive cisplatin-based Neoadjuvant Chemotherapy due to at least one of the following criteria: 7. Adequate Bone Marrow Function (without hematopoietic growth factor support within 14 days prior to study screening), defined as: 8. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance. 9. Adequate liver function, including: 10. Able to give informed consent and patient is willing and able to comply with scheduled study visits and treatment plan 11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. 12. Meeting the following criteria for sex specific considerations: 1. Males - for the duration of study and for at least 6 months after the last dose of study drug (Sasanlimab): 1. Refrain from donating sperm and be abstinent from intercourse OR Agree to use male condom and also consider the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant 2. Females:	1. Lymphadenopathy (\>1cm short-axis measurement on CT/MRI Imaging or biopsy proven) 2. Metastatic disease 3. Prior systemic chemotherapy for bladder cancer (however, may have had intra-vesical chemotherapy such as gemcitabine, docetaxel or mitomycin-C) 4. Prior treatment with systemic anti-cancer investigational agent 5. Other malignancy within 2 years prior to study screening, or active malignancy except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration) or other concurrent malignancy felt by the investigator has a very low likelihood to become metastatic 6. Previous radiation therapy to the bladder 7. Active or history of autoimmune disease which may deteriorate when receiving immune checkpoint blockade. 1. These autoimmune conditions include but are not limited to limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis 2. Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible. 8. Severe active infections (e.g., pulmonary tuberculosis) requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to study entry. 9. Clinically significant, multiple or severe drug allergies, intolerance to topical corticosteroids 10. Current unstable liver or biliary disease, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -e.g., presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody test result at screening) is acceptable. 11. Active, uncontrolled HIV/AIDS infection (well-controlled HIV patients may be allowed). 12. Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody. Note: prior intra-vesical BCG therapy is acceptable. 13. Prior treatment with immune-stimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)- γ. 14. Vaccination within 4 weeks from study screening and while on study treatment unless administration of inactivated vaccines. 15. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 16. Clinically significant (active) cardiovascular disease including the following: cerebral vascular accident/stroke \<6 months prior to screening; myocardial infarction \<6 months prior to screening; unstable angina; congestive heart failure (≥New York Heart Association Classification Class III); or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication. 17. Q-T interval corrected for heart rate (QTc) \>450 msec for male participants or QTc \>470 msec for female participants or QTc \>480 msec in participants with right bundle branch block 18. Prior organ transplantation or allogenic stem cell transplantation. 19. Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis. 20. Patients with intolerance to or who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or infused therapeutic proteins 21. Pregnant female patients; breastfeeding female patients; male patients able to father children and female patients of childbearing potential who are unwilling or unable to use a highly effective method(s) of contraception as outlined in this protocol for at least 6 months after the last dose of Sasanlimab (PF-06801591)

Inclusion Criteria

Exclusion Criteria

1. Capable of giving signed informed consent
2. Age ≥ 18 years
3. ECOG Eastern Cooperative Oncology Group performance status 0-2
4. Predominant (\>50%) urothelial carcinoma histology
5. Muscle-invasive bladder cancer (cT2-4a, cN0, cM0)
6. Decline/refuse OR Ineligible to receive cisplatin-based Neoadjuvant Chemotherapy due to at least one of the following criteria:
7. Adequate Bone Marrow Function (without hematopoietic growth factor support within 14 days prior to study screening), defined as:
8. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance.
9. Adequate liver function, including:
10. Able to give informed consent and patient is willing and able to comply with scheduled study visits and treatment plan
11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
12. Meeting the following criteria for sex specific considerations:
1. Males - for the duration of study and for at least 6 months after the last dose of study drug (Sasanlimab):
1. Refrain from donating sperm and be abstinent from intercourse OR Agree to use male condom and also consider the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
2. Females:

1. Lymphadenopathy (\>1cm short-axis measurement on CT/MRI Imaging or biopsy proven)
2. Metastatic disease
3. Prior systemic chemotherapy for bladder cancer (however, may have had intra-vesical chemotherapy such as gemcitabine, docetaxel or mitomycin-C)
4. Prior treatment with systemic anti-cancer investigational agent
5. Other malignancy within 2 years prior to study screening, or active malignancy except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration) or other concurrent malignancy felt by the investigator has a very low likelihood to become metastatic
6. Previous radiation therapy to the bladder
7. Active or history of autoimmune disease which may deteriorate when receiving immune checkpoint blockade.
1. These autoimmune conditions include but are not limited to limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
2. Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
8. Severe active infections (e.g., pulmonary tuberculosis) requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to study entry.
9. Clinically significant, multiple or severe drug allergies, intolerance to topical corticosteroids
10. Current unstable liver or biliary disease, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
* NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -e.g., presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody test result at screening) is acceptable.
11. Active, uncontrolled HIV/AIDS infection (well-controlled HIV patients may be allowed).
12. Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody. Note: prior intra-vesical BCG therapy is acceptable.
13. Prior treatment with immune-stimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)- γ.
14. Vaccination within 4 weeks from study screening and while on study treatment unless administration of inactivated vaccines.
15. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
16. Clinically significant (active) cardiovascular disease including the following: cerebral vascular accident/stroke \<6 months prior to screening; myocardial infarction \<6 months prior to screening; unstable angina; congestive heart failure (≥New York Heart Association Classification Class III); or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.
17. Q-T interval corrected for heart rate (QTc) \>450 msec for male participants or QTc \>470 msec for female participants or QTc \>480 msec in participants with right bundle branch block
18. Prior organ transplantation or allogenic stem cell transplantation.
19. Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
20. Patients with intolerance to or who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or infused therapeutic proteins
21. Pregnant female patients; breastfeeding female patients; male patients able to father children and female patients of childbearing potential who are unwilling or unable to use a highly effective method(s) of contraception as outlined in this protocol for at least 6 months after the last dose of Sasanlimab (PF-06801591)

Contacts and Locations

Principal Investigator

Raj Satkunasivam, MD

PRINCIPAL_INVESTIGATOR

Houston Methodist Hospital, Houston Methodist Research Institute

Study Locations (Sites)

Houston Methodist Hospital

Houston, Texas, 77006

United States

Collaborators and Investigators

Sponsor: The Methodist Hospital Research Institute

Raj Satkunasivam, MD, PRINCIPAL_INVESTIGATOR, Houston Methodist Hospital, Houston Methodist Research Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-15

Study Completion Date2027-04-01

Study Record Updates

Study Start Date2022-02-15

Study Completion Date2027-04-01

Terms related to this study

Keywords Provided by Researchers

Bladder Cancer
Muscle Invasive Bladder Cancer
Immune Checkpoint Inhibitor
Immunotherapy
Urothelial Carcinoma of the Bladder
Urologic neoplasms
Neoadjuvant therapy
Radiation
Stereotactic Body Radiation Therapy
Urinary Bladder Diseases
Urologic Diseases
Sasanlimab
Antineoplastic agents
Antineoplastic agents, Immunological

Additional Relevant MeSH Terms

Urothelial Carcinoma Bladder