Clinical trial NCT04620603: Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer
Official title: Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Cutaneous Malignant Melanoma
Renal Cell Cancer
Urothelial Cancer of Renal Pelvis
Keywords: Brachytherapy
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: 3 months after brachytherapy
measure: Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: 6 months after brachytherapy
measure: Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: 9 months after brachytherapy
measure: Number of participants with tumor response assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: 12 months after brachytherapy
measure: Number of participants with tumor response assessed by RECIST v1.1
timeFrame: 3 months after brachytherapy
measure: Number of participants with tumor response assessed by RECIST v1.1
timeFrame: 6 months after brachytherapy
measure: Number of participants with tumor response assessed by RECIST v1.1
timeFrame: 9 months after brachytherapy
measure: Number of participants with tumor response assessed by RECIST v1.1
timeFrame: 12 months after brachytherapy
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic, Case Comprehensive Cancer Center
name: Jay Ciezki, MD
role: PRINCIPAL_INVESTIGATOR
References: