Cryoablation With Pembrolizumab Or Avelumab In Urothelial Carcinoma

NCT04701918 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 20-531
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is examining the effectiveness of pembrolizumab plus cryoablation or aveluma plus cryoablation on people with urothelial carcinoma, including bladder cancer, that has spread.

Conditions

Bladder Cancer; Metastatic Urothelial Carcinoma

Keywords

Metastatic Urothelial Carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Evaluate objective response rate of non-ablated lesion(s) for combination pembrolizumab/avelumab and adjunctive cryoablation per RECIST v1.1 criteria

  up to 2 years

Secondary Outcomes (4)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  up to 2 years

• Progression-Free Survival (PFS)

  up to 2 years

• Overall survival (OS)

  up to 2 years

• Duration of response (DOR)

  up to 2 years

Study Arms (1)

Pembrolizumab/Avelumab + Cryoablation

EXPERIMENTAL

If patient is receiving pembrolizumab: Participants will be given 200 mg pembrolizumab intravenously once every 3 weeks. This will continue for up to 2 years as per standard of care. Participants will receive cryoablation between the 1st and 2nd doses of pembrolizumab. Cryoablation consists of using a CT scan to guide one or more thin needles to the tumor through your skin, where extreme cold is applied. If patient is receiving avelumab: Participants will be given 800 mg avelumab intravenously once every 2 weeks. This will continue for up to 2 years as per standard of care. Participants will receive cryoablation between the 1st and 2nd doses of avelumab. Cryoablation consists of using a CT scan to guide one or more thin needles to the tumor through your skin, where extreme cold is applied.

Drug: Pembrolizumab; Procedure: Cryoablation; Drug: Avelumab

Interventions

Pembrolizumab DRUG

Intravenous injection through a vein (IV) every 3 weeks

Also known as: Keytruda

Pembrolizumab/Avelumab + Cryoablation

Cryoablation PROCEDURE

Needle inserted through the skin and into the tumor using CT guidance

Pembrolizumab/Avelumab + Cryoablation

Avelumab DRUG

Intravenous injection through a vein (IV) every 2 weeks

Also known as: Bavencio

Pembrolizumab/Avelumab + Cryoablation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has read, signed and dated the Informed Consent Form (ICF), having been advised of the risks and benefits of the trial in a language understood by the subject.
• Age \> 18 years at date of ICF signature having the ability to comply with the protocol.
• Proof of medical insurance coverage.
• Histologically or cytologically documented metastatic (M1, Stage IV) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra)
• Measurable metastatic disease with at least one site of metastatic disease \> 2 cm in size and amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria. Metastasis sites amenable to cryoablation to include lymph node, peritoneum, liver, soft tissue, adrenal glands, kidney, lung, and bone. Must have measurable disease (by RECIST v1.1) independent of the lesion to be ablated (ie patient must have more than one metastasis)
• Life expectancy \> 12 weeks.
• PS ECOG 0 or 1
• Laboratory requirements:
• ANC \> 1 x 109/L
• Platelets \> 75 x 109/L
• ALT / AST \< 5 x ULN
• Total bilirubin \<3 mg/dL
• INR \<1.7
• CrCl \>30 ml/min

You may not qualify if:

• Lesion to undergo cryoablation cannot have had prior radiation therapy or other locoregional therapy
• Inability to lie flat for the cryoablation procedure.
• Known significant immunodeficiency due to underlying illness (e.g. HIV / AIDS) and/or blood CD4+ T cells \<200/ul
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, Guillain- Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this trial.
• Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this trial.
• Patients with history of vitiligo and controlled psoriasis are eligible for the trial.
• Continued adverse events from a previously administered chemotherapeutic agents.
• Grade 1 adverse events and ongoing toxicities such as alopecia are exempt
• Treatment with systemic corticosteroids exceeding the equivalent of 10 mg/day of prednisone or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
• Patients who receive acute, low-dose, systemic corticosteroid medications (e.g., a onetime dose of dexamethasone for nausea) or for prevention of hypersensitivity reactions to contrast agents may be enrolled in the trial.
• Anticoagulant or anti-platelet medication that cannot be interrupted prior to cryoablation
• Pregnant or lactating
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or that could affect the interpretation of the results or render the patient at high risk from treatment complications.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Biocompatibles UK Ltd: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

pembrolizumab; Cryosurgery; avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Eric Wehrenberg-Klee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 8, 2021
• Study Start: June 4, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)