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NCT Number: NCT04620603

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44122, United States

About this study

The purpose of this study is to evaluate the effect of combining LDR with immune checkpoint inhibition in stage III and IV melanoma, stage IV renal call cancer, and stage IV urothelial cancer. This involves the addition of a treatment called brachytherapy to SOC immunotherapy. Brachytherapy is a form of radiation therapy where radioactive pellets are placed within a tumor to temporarily irradiate the tumor at a low level. This is the first time that this combination (immunotherapy and brachytherapy) has been used in humans.

The objectives of this study are to evaluate the effect of combining LDR with immunotherapy, determine safety and feasibility, generate a toxicity profile, evaluate response, and overall survival.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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:
  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Low Dose Rate Brachytherapy (LDR)

Radiation

LDR on treatment day 1

Standard-of-Care Immunotherapy

Drug

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

Primary outcomes

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

    Time frame: 3 months after brachytherapy

    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

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

    Time frame: 6 months after brachytherapy

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

    Time frame: 9 months after brachytherapy

    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

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

    Time frame: 12 months after brachytherapy

    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

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

    Time frame: 3 months after brachytherapy

    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

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

    Time frame: 6 months after brachytherapy

    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

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

    Time frame: 9 months after brachytherapy

    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

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

    Time frame: 12 months after brachytherapy

    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

Sponsors and collaborators

Lead sponsor

Case Comprehensive Cancer Center

Other

Registry information

Important dates

Study start
2021
Primary completion
2024
Study completion
2026
First posted
Nov 9, 2020
Registry last updated
May 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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