Trial Title:
Dose-escalation Study of Ultra-high Dose Ablative Radiosurgery With Immunotherapy for Bulky Metastatic Cancer Patients
NCT ID:
NCT06416436
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasm Metastasis
Atezolizumab
Conditions: Keywords:
Stereotactic Ablative Radiotherapy
SBRT
Atezolizumab
Tecentriq
Metastatic
Phase I
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Traditional 3+3 model
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab will be administered at a fixed dose of 1680 mg IV route every 4 weeks (1680
mg on Day 1 of each 28-day cycle), which is an approved dosage for atezolizumab, as
outlined in the prescribing information.
Arm group label:
SBRT with concurrent and adjuvant atezolizumab immunotherapy
Intervention type:
Radiation
Intervention name:
Stereotactic Ablative Radiotherapy (SBRT)
Description:
Ultra-High Doses of Ablative Radiosurgery
SBRT is delivered to metastases over 3-5 fractions within 1-2 weeks
Arm group label:
SBRT with concurrent and adjuvant atezolizumab immunotherapy
Summary:
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.
Detailed description:
Patients that provide informed consent will undergo a 30-day screening period to
determine eligibility for the trial. If eligible, patients will begin treatment on SBRT
(delivered to metastases over 3-5 fractions within 1-2 weeks) with concurrent and
adjuvant atezolizumab (1680 mg on Day 1 of each 28-day cycle) immunotherapy regimen for
up to one year.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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:
1. Leukocytes ≥ 3K/µL
2. Lymphocyte count ≥ 0.5 x 10^9/L (500/µL)
3. 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
4. Platelets ≥100K/μL) without transfusion
5. Hemoglobin ≥ 9 g/dL
6. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) [calculated using the
Cockcroft-Gault formula]
7. Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN. Participants with
known Gilbert disease: serum bilirubin ≤ 3 x ULN
8. Serum albumin ≥ 35 g/L (3.5 g/dL)
9. 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
10. For participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x
ULN
11. For participants receiving therapeutic anticoagulation: stable anticoagulant
regimen
12. 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.
13. 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.
14. Negative hepatitis B surface antigen (HbsAg) test at screening. Negative total
hepatitis B core antibody (HbcAb) test at screening, or positive total HbcAb
test followed by a negative hepatitis B virus (HBV) DNA test at screening. The
HBV DNA test will be performed only for participants who have a negative HbsAg
test and a positive total HbcAb 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.
15. Women of child-bearing potential and men with partners of child-bearing
potential must agree to practice sexual abstinence or to use the forms of
contraception listed in Child-Bearing Potential/Pregnancy section and below for
the duration of study participation and for 180 DAYS/6 MONTHS following
completion of therapy. Men must refrain from donating sperm during this same
period.
1. A woman is considered to be of childbearing potential if she is
postmenarchal, has not reached a postmenopausal state (≥ 12 continuous
months of amenorrhea with no identified cause other than menopause), and
has not undergone surgical sterilization (removal of ovaries, fallopian
tubes and/or uterus) or another cause as determined by the investigator
(e.g., Müllerian agenesis). Per this definition, a woman with a tubal
ligation is considered to be of childbearing potential. The definition of
childbearing potential may be adapted for alignment with local guidelines
or requirements.
2. Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
3. The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle
of the participant. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not adequate
methods of contraception. If required per local guidelines or regulations,
locally recognized adequate methods of contraception and information about
the reliability of abstinence will be described in the local Informed
Consent Form.
Exclusion Criteria:
- 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
1. Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
2. Asymptomatic participants with treated CNS lesions are eligible, provided that
all of the following criteria are met:
1. Measurable disease, per RECIST v1.1, must be present outside the CNS
2. The participant has no history of intracranial hemorrhage or spinal cord
hemorrhage
3. 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.
4. The participant has no ongoing requirement for corticosteroids as therapy
for CNS disease
5. 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:
1. Participants with a history of autoimmune-related hypothyroidism who are on
thyroid-replacement hormone are eligible for the study
2. Participants with controlled Type 1 diabetes mellitus who are on an insulin
regimen are eligible for the study
3. Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., participants with psoriatic arthritis
are excluded) are eligible for the study provided all of following conditions
are met:
1. Rash must cover < 10% of body surface area
2. Disease is well controlled at baseline and requires only low-potency
topical corticosteroids
3. There has been no occurrence of acute exacerbations of the underlying
condition requiring psoralen plus ultraviolet A radiation, methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors, or high-potency
or oral corticosteroids within the previous 12 months
4. See also Appendix D for list of autoimmune diseases and immune deficiencies
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
- Active tuberculosis
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment, or anticipation of need for a major surgical
procedure during the study
- Severe infection within 4 weeks prior to initiation of study treatment, including,
but not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia, or any active infection that could impact participant safety
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment. Participants receiving prophylactic antibiotics (e.g., to
prevent a urinary tract infection or chronic obstructive pulmonary disease
exacerbation) are eligible for the study.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, or may render the participant at high risk
from treatment complications
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of
study treatment, or anticipation of need for such a vaccine during atezolizumab
treatment or within 5 months after the final dose of atezolizumab
- Current treatment with anti-viral therapy for HBV
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
- Prior treatment with checkpoint blockade therapy
- History of prior immunotherapy induced pneumonitis and/or peritonitis that is Grade
≥3 is not permitted (instance of Grade 1 or 2 that have fully recovered and
tolerated subsequent immunotherapy is permitted)
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need for systemic immunosuppressive medication during study
treatment, with the following exceptions:
1. Participants who received acute, low-dose systemic immunosuppressant medication
or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48
hours of corticosteroids for a contrast allergy) are eligible for the study
2. Participants who received mineralocorticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or
low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency
are eligible for the study
- History of severe allergic anaphylactic reactions to chimeric or humanized
antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
- Known allergy or hypersensitivity to any component of the atezolizumab formulation
- Has a known allergic reaction to any excipient contained in the study drug
formulation
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Kansas Medical Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Contact:
Last name:
Nurse Navigator
Phone:
913-945-7552
Email:
CTNurseNav@kumc.edu
Start date:
May 23, 2024
Completion date:
July 1, 2027
Lead sponsor:
Agency:
University of Kansas Medical Center
Agency class:
Other
Source:
University of Kansas Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06416436
https://clinicaltrials.gov/ct2/show/NCT02608385
https://pubmed.ncbi.nlm.nih.gov/23230000/
https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-hemophagocytic-lymphohistiocytosis
