Clinical trial NCT04376502: Immune Checkpoint Inhibitor and MR-guided SBRT for Limited Progressive Metastatic Carcinoma.
Official title: Phase II Trial of Immune Checkpoint Inhibitor and Novel in Situ Radiation "Booster Shot" Tumor Vaccination in Patients With Metastatic Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Metastatic Carcinoma
Keywords: radiation
Lead sponsor: Baptist Health South Florida
Sponsor class: OTHER
Collaborators: name: Viewray Inc.
First posted: 2020-05-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 Immune checkpoint inhibitor is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions).
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria
timeFrame: 6 months
Secondary outcomes:
measure: Number of Treatment Related Adverse Events
timeFrame: through study completion, an average of 1 year
measure: Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC)
timeFrame: 6 month
measure: Duration of Response
timeFrame: 6 month
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Progression-free Survival (PFS)
timeFrame: 6 month
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health South Florida
state: Florida
Study officials:
affiliation: Miami Cancer Institute (MCI) at Baptist Health, Inc.
name: Michael D Chuong, MD
role: PRINCIPAL_INVESTIGATOR
References: