Dose-escalation Study of Ultra-high Dose Ablative Radiosurgery With Immunotherapy for Bulky Metastatic Cancer Patients

Withdrawn before enrolling · Phase 1

Conditions studied: Solid Tumor

In brief

The purpose of this study is to determine whether cytoreduction of bulky metastatic disease using ultra high dose SBRT in combination with immunotherapy is tolerable and feasible In patients who have exhausted SoC treatment options.

Key facts

Study ID

NCT06416436

Run by

University of Kansas Medical Center

People needed

0

Starts

2024-07-15

Expected to finish

2024-07-15

Last updated by the study team

2025-06-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability of participant to understand this study, and participant willingness to sign a written informed consent
• Males and females age ≥ 18 years
• Measurable disease by RECIST 1.1 Participants must have at least two radiographically identifiable lesions measurable by RECIST v1.1 criteria and one of those lesions must be ≥65 cc. NOTE: 'cc' equals (width x length x height)/2 to provide rough approximation. For example, a 5.1 x 5.1 x 5.1 cm tumor would be 66.3 cc and appropriate for trial enrollment
• Participants must have washout period of 5 elimination half-lives or 28 days (whichever is longer) from time of last systemic therapy to start of study treatment
• Women of childbearing potential must have a negative serum pregnancy test at time of enrollment (at screening and up to 48 hours prior to start of radio- or immuno- therapy)
• Participants with biopsy and radiographically confirmed metastatic cancer (i.e., Lung, head and neck, ovarian, colorectal, sarcoma)
• At least 1st line (1L) systemic therapy or immunotherapy must have failed for participants and standard of care therapy options must also be exhausted. Standard of care options that have been discontinued for reasons other than disease progression are eligible. NOTE: Participants who are off systemic therapy who are being monitored with surveillance imaging, who then develop disease progression and are without standard of care therapy options are eligible for enrollment.
• At least one lesion (and up to a maximum of four lesions) must be ≥65 cc (calculated using tumor length x width x height to closest approximation)
• Prior RT is permitted if the lesion to be treated and surrounding region (no appreciable dosimetric overlap, assessed on case-by-case basis as needed) with ultra-high dose SBRT was not previously treated
• Participants with CNS metastatic disease will be allowed on protocol if all lesions are managed prior to starting extra-CNS ablative therapy
• Availability of a representative (FFPE) tumor specimen from metastatic diagnosis of cancer done prior to any study intervention for exploratory study-related biomarker research
• Adequate organ function, defined as the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Leukocytes ≥ 3K/µL
• Lymphocyte count ≥ 0.5 x 10\^9/L (500/µL)
• Absolute Neutrophil Count ≥1.5K/µL without granulocyte colony-stimulating factor support. NOTE: Participants with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the participant
• Platelets ≥100K/μL) without transfusion
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) [calculated using the Cockcroft-Gault formula]
• Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN. Participants with known Gilbert disease: serum bilirubin ≤ 3 x ULN
• Serum albumin ≥ 35 g/L (3.5 g/dL)
• Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
• For participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load. *** NOTE: A participant may be eligible if test is positive and will be left to the investigator to determine appropriateness for trial enrollment if medically stable and without signs of active, uncontrolled disease. Prior to formal enrollment, please contact protocol study PI to review.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for participants who have a positive HCV antibody test.*** NOTE: A participant may be eligible if test is positive and will be left to the investigator to determine appropriateness for trial enrollment if medically stable and without signs of active, uncontrolled disease. Prior to formal enrollment, please contact protocol study PI to review.

You may not qualify if…

• Simultaneously enrolled in any therapeutic clinical trial
• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Is pregnant or breastfeeding
• Female of childbearing potential planning to become pregnant while receiving study treatment or for less than 180 DAYS/6 MONTHS after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result at time of enrollment (at screening and up to 48 hours prior to start of radio- or immuno- therapy).
• Male of childbearing potential planning to father a child or donate sperm while receiving study treatment or for less than 180 DAYS / 6 MONTHS after the last dose of study treatment
• Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
• COVID-19: Participants with active COVID-19 symptoms and/or hospitalized for severe or critical COVID-19 symptoms
• Participants with uncontrolled concurrent illness or infection (i.e., active pneumonia or infection)
• Participants with only bone metastatic disease
• Immunosuppressive disorders (i.e., solid organ transplant recipient, allogeneic stem cell transplant) (please refer Appendix D for full list)
• Participants who are enrolled in hospice or felt to have less than 6 months life expectation
• Uncontrolled or untreated CNS metastases
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Asymptomatic participants with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS
• The participant has no history of intracranial hemorrhage or spinal cord hemorrhage
• The participant has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
• The participant has no ongoing requirement for corticosteroids as therapy for CNS disease
• If the participant is receiving anti-convulsant therapy, the dose is considered stable
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). • Participants with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN
• Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, scleroderma, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

Where it is running

• The University of Kansas Medical Center — Kansas City, Kansas, United States

Full record on ClinicalTrials.gov

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