Immune Checkpoint Inhibitor and MR-guided SBRT for Limited Progressive Metastatic Carcinoma.

Phase II Trial of Immune Checkpoint Inhibitor and Novel in Situ Radiation "Booster Shot" Tumor Vaccination in Patients With Metastatic Carcinoma

This is an open label single arm phase 2 clinical trial in patients with metastatic solid malignancy of any histology who have previously experienced limited progression in at least 1 and up to 5 lesions while on immune checkpoint inhibitors monotherapy.

Study Overview

• Status: Terminated
• Conditions: Metastatic Carcinoma
• Intervention / Treatment: Radiation: Radiation Therapy

Detailed Description

All potential subjects are required to undergo screening evaluation to determine eligibility within 28 days of study enrollment.

Eligible subjects will continue the same immune checkpoint inhibitors on which they experienced limited progression and will also receive radiation therapy. radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference, and after a 1-week interval during which immune checkpoint inhibitor is continued alone, radiation therapy will be given to a second and separate tumor. No additional radiation therapy will be delivered. immune checkpoint inhibitors will be continued until disease progression or unacceptable toxicity. Diagnostic imaging studies will be performed to determine treatment response at baseline/screening, 8 weeks after initiation of radiation therapy to the first lesion and every 8 weeks thereafter.

Peripheral blood mononuclear cell composition will be evaluated at various time points within 14 days of starting radiation therapy, on Day 8 (1 week after starting radiation therapy to the first lesion), Day 23 (1 week after starting radiation therapy to the second lesion), and 8 weeks after treatment initiation.

A total of 52 subjects will be enrolled on this trial. The expected rate of accrual is 2 patients per month at a single institution over 26 months.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age at the time of study entry.
2. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
3. Life expectancy of .12 weeks as estimated by the treating physician.
4. Metastatic carcinoma confirmed by biopsy or imaging study if biopsy is not deemed feasible.
5. Most recent anti-cancer therapy consists of a single ICI drug including but not limited to ipilimumab, nivolumab, pembrolizumab, atezolizumab.
6. Radiographic evidence of progression while on a single ICI drug in 1 and up to 5 lesions.
7. Eligible to continue ICI during and after radiation therapy.
8. 3 radiographically distinct and measurable lesions (primary and/or metastatic lesions) by RECIST 1.1 criteria, with .3 lesions separated from each other by .5 cm
9. Subjects must consent to all study procedures described in the protocol including radiographic evaluation and blood draws.
10. Immunosuppressive doses of systemic medication including steroids must be discontinued at least 14 days prior to the start of radiation therapy.
11. Adequate normal organ and marrow function
12. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: .60 years old and no menses for .1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy), have a negative serum pregnancy test within 14 days of study enrollment, and not be breastfeeding.

Exclusion Criteria:

1. Any contraindication to having an MRI scan.
2. Chemotherapy, biologic agent, investigational therapy, or radiation therapy given within 14 days of study enrollment.
3. Symptomatic or uncontrolled brain metastasis requiring treatment.
4. The need for palliative radiation therapy to a non-target lesion prior to radiation therapy to one of 2 target lesion on this study.
5. Prior radiation therapy to any lesion that would receive radiation therapy on this protocol.
6. Prior radiation therapy to a lesion located within 4 cm of previously irradiated structures: spinal cord that previously received >45 Gy; brachial plexus that previously received >45 Gy; small/large intestine or stomach that previously received >45 Gy; prior total lung V20 >30%.
7. Prior radiation therapy that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator.

8. History of any primary malignancy with the exception of

   1. Malignancy treated with curative intent and with no known active disease for at least 3 years before enrollment on this study.
   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
   3. Adequately treated carcinoma in situ without evidence of disease (i.e. cervical carcinoma in situ; superficial bladder cancer).
9. Any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 > grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to worsen by treatment on this study are permitted to enroll on this study.
10. Active or prior documented autoimmune disease within the past 2 years. Subjects with vitiligo, type I diabetes mellitus, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
11. Subjects requiring systemic corticosteroid (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of study enrollment.
12. Contraindication to IV contrast despite premedication for iodine allergy, which would limit the ability to assess radiographic response to study treatment.
13. Prior allogeneic organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: radiation therapy (RT); RT for all subjects will consist of treating one tumor of the treating physician's preference (40 Gy in 5 fractions), and after a 1-week interval during which Immune checkpoint inhibitor (ICI) is continued alone, RT will be given to a second and separate tumor (30 Gy in 5 fractions).	Radiation: Radiation Therapy; Radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference (40 Gray (Gy) in 5 fractions), and after a 1-week interval during which ICI is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria	ORR is defined as the percent of participants who have a partial response (PR) or complete response (CR) to therapy of non-irradiated lesions according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria assessed on CT imaging. CR is defined as the disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of the longest diameters of target lesions AND for non-target lesions, no progression of existing lesions or appearance of new lesions.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Related Adverse Events	Treatment related adverse events are defined as those possibly, probably, or definitely related to the study treatment. These events will be tabulated and reported by grade of severity.	through study completion, an average of 1 year
Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC)	irORR is the percent of patients with best overall response of irCR or irPR from the start of the study until 6 months later. Only index and measurable new lesions are taken into account in irRC and response is defined over at least 4 weeks. irCR is defined as the disappearance of all lesions in two observations at least 4 weeks apart. irPR is defined as at least 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.	6 month
Duration of Response	Duration of response is defined as the time from when CR or PR is first determined until the first date of documented progressive disease (PD) or death, whichever occurs first.	6 month
Overall Survival (OS)	OS is defined as the percent of participants who are alive at the end of the study. Death due to any cause will be considered.	2 years
Progression-free Survival (PFS)	PFS is defined as the amount of time from first treatment to disease progression or death from any cause.	6 month

Collaborators and Investigators

• Sponsor: Baptist Health South Florida
• Collaborators: Viewray Inc.
• Investigators: Principal Investigator: Michael D Chuong, MD, Miami Cancer Institute (MCI) at Baptist Health, Inc.

Publications and helpful links

Helpful Links

• Miami Cancer Institute Website

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: radiation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma
• Other Study ID Numbers: 2018-CHU-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No