Trial Title:
Pembrolizumab and EV With Radiation Therapy for MIBC Patients (PEVRAD)
NCT ID:
NCT05879653
Condition:
Bladder Cancer
Conditions: Official terms:
Urinary Bladder Neoplasms
Pembrolizumab
Conditions: Keywords:
Bladder preservation
Radiation therapy
Immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MK-3475
Description:
During the induction phase, MK-3475 200 mg will be administered as four cycles of 3-weeks
regimen, with ASG-22CE 1.25 mg/kg administered on Day 1 and Day 8 of each cycle. The
treatment and maintenance phases will consist of 9 cycles of one course per 6 weeks, with
MK-3475 400 mg administered on Day 1 of each course at Q6W.
Arm group label:
MK-3475 and ASG-22CE With Radiation Therapy
Other name:
Pembrolizumab
Intervention type:
Drug
Intervention name:
ASG-22CE
Description:
During the induction phase, four cycles of 3-weeks regimen are administered, with
ASG-22CE 1.25 mg/kg administered on Day 1 and Day 8 of each cycle.
Arm group label:
MK-3475 and ASG-22CE With Radiation Therapy
Other name:
Enfortumab vedotin
Intervention type:
Procedure
Intervention name:
maximal TURBT
Description:
All participants who were not determined to have PD on imaging during the induction phase
should have had a maximal TURBT performed at 13 (± 1week) weeks after the first dose of
trial drug.
Arm group label:
MK-3475 and ASG-22CE With Radiation Therapy
Intervention type:
Radiation
Intervention name:
Radiation therapy
Description:
Radiotherapy will be initiated no later than 8 weeks after maximal TUR-BT. In this trial,
a total dose of 56 Gy will be delivered using 2 Gy per dose. 40 Gy/20 fr (2 Gy/fr) to the
small pelvis followed by 16 Gy /8 fr (2 Gy/fr) to the whole bladder 5 times a week for 5
consecutive days using Three-Dimensional Conformal Radiation Therapy (3D-CRT).
Arm group label:
MK-3475 and ASG-22CE With Radiation Therapy
Summary:
This study is designed to assess the efficacy and safety of induction therapy with
MK-3475 and ASG-22CE and radiation therapy with MK-3475 in patients with cT2-4aN0M0
muscle invasive bladder cancer who are unfit for or refuse radical cystectomy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Male/female participants who are at least 18 years of age on the day of signing
informed consent and who have a first confirmed diagnosis of MIBC with
predominant urothelial histology obtained via a diagnostic or maximal TURBT
within 90 days prior to enrollment.
Note: Participants with mixed histology are eligible provided the urothelial
component is ≥50%.
2. Has clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT
of the chest and CTU/MRU of abdomen and pelvis), assessed by the site.
3. Male participants:
A male participant must agree to use a contraception and not to donate sperm
during the administration of MK-3475 and ASG-22CE and for at least 90 days
after the last dose of MK-3475 and for 6 months after ASG-22CE.
4. Female participants:
A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance during the
treatment period and for at least 120 days after the last dose of MK3475
and for 6 months after ASG-22CE and RT.
5. The participant provides written informed consent for the trial.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the first dose of
study intervention.
7. Demonstrates adequate organ function. All screening laboratory tests should be
performed within 10 days prior to the first dose of study intervention.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Has the presence of diffuse CIS (multiple foci [4 or greater] of CIS) throughout the
bladder.
2. Has the presence of UC at any site outside of the urinary bladder in the previous 2
years except for Ta/T1/CIS of the upper tract if the patient has undergone a
complete nephroureterectomy.
3. Has the presence of any small cell or neuroendocrine component in the tumor tissue
sample.
4. Has a known additional malignancy that is progressing or has required active therapy
within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, superficial bladder cancer or other carcinoma in situ (eg, breast
carcinoma, cervical cancer in situ) who have undergone potentially curative therapy
are not excluded. Participants with low-risk prostate cancer (T1-T2a, Gleason score
≤6, and PSA <10 ng/mL) either treated with definitive intent any time before
screening or untreated in active surveillance are not excluded.
5. Has limited bladder function with frequency of small amounts of urine (< 30 mL),
urinary incontinence, or requires self-catheterization or a permanent indwelling
catheter.
6. Has a history of radiation therapy to the pelvic region for any reason.
Prior/Concomitant Therapy
7. Has received prior pelvic/local radiation therapy or any antineoplastic treatment
for MIBC.
Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG
or intravesical chemotherapy is permitted, but must be completed ≥28 days before the
first dose of the trial drug. Prior systemic treatment received for treatment of
NMIBC is not permitted.
8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX-40, CD137).
9. Has received prior therapy with an ASG-22CE or other MMAE-containing ADCs.
10. Has received a live vaccine or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of killed vaccines is allowed.
Note: please refer to Section 5.5 for information on COVID-19 vaccines
Prior/Concurrent Clinical Study Experience
11. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 3 months before the first dose of
study intervention.
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
Diagnostic Assessments
12. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first
dose of study intervention (see Appendix 3). If the urine test is positive or cannot
be confirmed as negative, a serum pregnancy test will be required.
13. Has uncontrolled diabetes. Uncontrol diabetes is defined as hemoglobin A1c (HbA1c)
≥8% or HbA1c 7% to <8% with associated diabetes symptoms (polyuria or polydipsia)
that are not otherwise explained.
14. Has ongoing sensory or motor neuropathy Grade 2 or higher.
15. Has active keratitis or corneal ulceration. Subjects with superficial punctate
keratitis are allowed if the disorder is being adequately treated in the opinion of
the investigator.
16. Has received prior radiotherapy within 2 weeks of start of study intervention or
radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of
palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
17. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of trial drug.
18. Has severe hypersensitivity (≥Grade 3) to MK-3475, ASG-22CE and/or any of their
excipients.
19. Has active autoimmune disease that has required systemic treatment in the past 2
years except replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid).
20. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
21. Has an active infection requiring systemic therapy.
22. Has a known history of Human Immunodeficiency Virus (HIV) infection. The test should
be performed within 28 days prior to the first dose of the trial drug.
23. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA)
and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA)
infection. The test should be performed within 28 days prior to the first dose of
the trial drug.
24. Has not adequately recovered from major surgery or has ongoing surgical
complications.
25. Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating investigator.
26. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
27. Pregnant or lactating, or female patients or male patients who wish to become
pregnant from the time of screening to 120 days after the last dose of MK-3475 and 6
months after radiotherapy and the last dose of ASG-22CE, or their partners.
28. Has had an allogenic tissue/solid organ transplant.
29. Has a documented history of a cerebral vascular event (stroke or transient ischemic
attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with
NYHA Class IV within 6 months prior to the first dose of the trial drug.
30. Or, if participation in this clinical trial is considered inappropriate according to
the judgment of the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Kobe City Medical Center General Hospital
Address:
City:
Kobe
Zip:
650-0047
Country:
Japan
Status:
Recruiting
Facility:
Name:
University of Tsukuba Hospital
Address:
City:
Tsukuba
Zip:
305-8576
Country:
Japan
Status:
Recruiting
Facility:
Name:
Kyoto University Hospital
Address:
City:
Kyoto
Zip:
606-8507
Country:
Japan
Status:
Recruiting
Facility:
Name:
Osaka Metropolitan University Hospital
Address:
City:
Osaka
Zip:
545-8586
Country:
Japan
Status:
Recruiting
Start date:
October 1, 2023
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Kyoto University Hospital
Agency class:
Other
Collaborator:
Agency:
University of Tsukuba
Agency class:
Other
Collaborator:
Agency:
Osaka Metropolitan University
Agency class:
Other
Collaborator:
Agency:
Kobe City Medical Center General Hospital
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Astellas Pharma Inc
Agency class:
Industry
Source:
Kyoto University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05879653
