Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer

NCT04620603 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE6620
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study of combination low dose rate brachytherapy (LDR) added to standard of care (SOC) immunotherapy in stage III and IV melanoma, stage IV renal call cancer, and stage IV urothelial cancer.

Conditions

Cutaneous Malignant Melanoma; Renal Cell Cancer; Urothelial Cancer of Renal Pelvis

Keywords

Brachytherapy

Outcome Measures

Primary Outcomes (8)

• Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

  iRECIST was developed by the RECIST working group for the use of RECIST version 1.1 in cancer immunotherapy trials, to ensure consistent design and data collection. ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  3 months after brachytherapy

• Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

  iRECIST was developed by the RECIST working group for the use of RECIST version 1.1 in cancer immunotherapy trials, to ensure consistent design and data collection. ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  6 months after brachytherapy

• Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

  iRECIST was developed by the RECIST working group for the use of RECIST version 1.1 in cancer immunotherapy trials, to ensure consistent design and data collection. ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  9 months after brachytherapy

• Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

  iRECIST was developed by the RECIST working group for the use of RECIST version 1.1 in cancer immunotherapy trials, to ensure consistent design and data collection. ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  12 months after brachytherapy

• Number of participants with tumor response assessed by RECIST v1.1

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (iRECIST or RECIST v1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  3 months after brachytherapy

• Number of participants with tumor response assessed by RECIST v1.1

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  6 months after brachytherapy

• Number of participants with tumor response assessed by RECIST v1.1

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  9 months after brachytherapy

• Number of participants with tumor response assessed by RECIST v1.1

  ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

  12 months after brachytherapy

Study Arms (1)

LDR + SOC Immunotherapy

EXPERIMENTAL

Participants will receive one treatment of brachytherapy on treatment day 1 (LDRD1). After a minimum of 7 days but no more than 30 days to allow antigenic release, participants will then begin immunotherapy treatment with SOC immunotherapy at the standard FDA-approved dose. Standard immunotherapy will be administered on D1 of every standard of care cycle (either 14, 21, 28, or 42 day cycle) at the standard dose. Participants can receive up to 1 year of SOC immunotherapy.

Radiation: Low Dose Rate Brachytherapy (LDR); Drug: Standard-of-Care Immunotherapy

Interventions

Low Dose Rate Brachytherapy (LDR) RADIATION

LDR on treatment day 1

LDR + SOC Immunotherapy

Standard-of-Care Immunotherapy DRUG

Standard or care immunotherapy will be administered at the FDA approved dose via IV infusion.

LDR + SOC Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed unresectable stage III or stage IV cutaneous melanoma, stage IV renal cell cancer, and stage IV urothelial cancer.
• ECOG performance status 0-2.
• Have measurable disease per RECIST v1.1 or iRECIST. Refer to Appendix B
• Have the following clinical laboratory values:
• Absolute neutrophil count (ANC) ≥ 1500/ μL
• Hgb ≥ 9 g/dL
• Platelet count ≥ 75, 000/ μL
• Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
• AST and ALT ≤ 2x ULN
• Serum Creatinine \< 2x ULN
• Female participants who:
• Are postmenopausal for at least 1 year before entering the screening visit, OR
• Are surgically sterile, OR
• Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose.
• Male participants who:

You may not qualify if:

• Participants diagnosed with uveal melanoma
• Participants who have been treated with whole head radiation for brain metastases
• Invasive cancers not being treated on this trial (i.e. lymphoma that received systemic therapy) diagnosed \< 3 years prior that required systemic treatment. This is intended to include a patient with melanoma who was diagnosed \< 3 years prior to screening for this trial that has received antecedent systemic therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prior anti-cancer therapy for melanoma, renal cell cancer, or urothelial cancer less than 14 days prior to first dose of study treatment.
• Pregnant or nursing females
• Unwilling or unable to follow protocol requirements.
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study treatment.
• Other active non-melanoma, non-renal cell, or non-urothelial metastatic cancers requiring systemic treatment.
• Participants currently receiving systemic corticosteroids doses over 15mg prednisone or equivalent.
• Participants with uncontrolled HIV or hepatitis.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44122, United States

Location

MeSH Terms

Conditions

Melanoma, Cutaneous Malignant; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Jay Ciezki, MD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 9, 2020
• Study Start: May 27, 2021
• Primary Completion: March 20, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)