Trial Title:
vGRID SBRT: A Phase I Clinical Trial in Unresectable or Metastatic HCC
NCT ID:
NCT05727787
Condition:
Liver Cancer
Conditions: Official terms:
Liver Neoplasms
Conditions: Keywords:
Liver Cancer
SBRT
Radiation Treatment
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Treatment
Description:
Single fraction SBRT 27 Gy
Arm group label:
Single fraction SBRT 27 Gy
Summary:
This trial will provide the maximum tolerated dose for radiation therapy for liver tumors
and describe the toxicity profile using the vGRID therapy technique. Based on trials
using this type of radiation in other cancers demonstrating low toxicity rates even with
very high radiation doses and high efficacy, it is likely that vGRID therapy in this
trial will be well tolerated and allow dose escalation beyond currently common doses for
liver tumors.
Detailed description:
While 30 Gy in a single-dose SBRT has been demonstrated to be safe for liver tumors,
higher radiation dose is likely required to control larger tumors. Radiation dose
escalation beyond 30 Gy to the entire tumor will be significantly limited by potential
toxicity to nearby tissues and organs. vGRID therapy, which treats part of the tumor to a
high dose while the rest of the tumor to a lower dose, may allow safe dose escalation
beyond 30 Gy. As described above, our treatment planning simulation has demonstrated an
ability to safely dose escalate using the vGRID technique while keeping radiation doses
to surrounding tissues and organs to lower than well-accepted dose limits.
The overall goal of this study is to assess the MTD of SBRT to live tumors using the
vGRID radiation technique. We have specifically chosen dose level 1 to be 27 Gy (below
the 30 Gy SBRT dose used in the trial by Goodman et al which was demonstrated to be
safe). Further, this dose of 27 Gy x 1 will have a point dose biological equivalent dose
(BED) of 100 (using alpha/beta ratio of 10), similar to the BED of 100 used in the
cooperative group trial RTOG 1112 for HCC. While unlikely, if DLT's are experienced in
our lowest dose cohort, we will de-escalate radiation dose to 40 Gy in 5 fractions (BED
72) which was previously shown to be safe in Child's Pugh Class B patients, with a 2 year
LC of 90% (Andolino IJROBP 2011).
The dose levels for this phase I trial are: 1) 27 Gy, 2) 32 Gy, 3) 37 Gy, 4) 42 Gy, 5) 47
Gy. Our third highest dose of 37 Gy x1 has a BED of 173.9 (alpha/beta ratio of 10), which
is similar to Rusthoven's 60 Gy in 3 fractions for liver metastases (Rusthoven JCO 2009).
Our highest dose cohort is 47 Gy x 1, which has a BED of 267.9 to the tumor, will
represent significant dose escalation compared to current treatment (2.7x the biological
dose to tumor), and if found to be safe, will be used for the future Phase II trial.
This trial will provide the MTD for radiation therapy for liver tumors and describe the
toxicity profile using the vGRID therapy technique. Based on trials using this type of
radiation in other cancers demonstrating low toxicity rates even with very high radiation
doses and high efficacy, it is likely that vGRID therapy in this trial will be well
tolerated and allow dose escalation beyond currently common doses for liver tumors.
The safety of this trial is maximized by treatment planning following strict dose limits
to nearby tissues and organs. Even though part of the tumor will receive dose escalated
vGRID radiation, treatment plans must meet strict criteria regarding dose limits to
nearby tissues and organs that are known to be safe to patients.
Upon completion of vGRID radiation, patients will than begin treatment standard of care
treatment option Atezolizumab. The rationale for following vGRID radiation followed
Atezolizumab is to potentiate the immune microenvironment and enhance synergy of
anti-tumor effect.
Atezolizumab is often given with bevacizumab per the landmark study IMbrave150 in
unresectable HCC patients (Finn RS NEJM 2020). However, given the added risk of GI
toxicity from bevacizumab with radiation, we have stipulated in this trial to hold
bevacizumab with cycle 1 of atezolizumab, which is to begin 12 - 16 days after completion
of radiation.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Ability of participant OR Legally Authorized Representative (LAR) to understand this
study, and participant or LAR willingness to sign a written informed consent .
2. Males and females age ≥ 18 years.
3. ECOG Performance Status 0 - 1
4. Histologically confirmed hepatocellular carcinoma (HCC) or mixed HCC and
cholangiocarcinoma either locally advanced or metastatic.
5. Not a candidate for surgical resection, or transplant
6. Child Pugh A - B7 liver function scale classification 14 days prior to entry.
7. Unresectable, locally-advanced or metastatic hepatocellular carcinoma. Meets normal
liver and adjacent organ radiation dose constraints, which usually corresponds to
tumor sizes 4 - 12 cm in diameter. Tumors that are larger than 12cm are permitted
provided radiation dose constraints to adjacent normal tissue are met per radiation
dose constraint table
8. Women of childbearing potential must have a negative serum pregnancy test 48 hours
prior to initiating study intervention. Women of child-bearing potential and men
with partners of child-bearing potential must agree to practice sexual abstinence,
or to use an acceptable form of contraception for the duration of study
participation, and for at least 12 months following completion of therapy. Men of
child-bearing potential must agree not to donate sperm while on this study and for
at least 12 months after their last study treatment.
Adequate organ function, defined as follows: Result Date
9. Hemoglobin ≥8 g/dL (The use of transfusion is acceptable)
10. Absolute Neutrophil Count > 1.0 K/UL
11. Platelets > 50 K/UL
12. AST and ALT < 6 times upper limit of normal (ULN)
13. Albumin >2.9g/dl
14. Prothrombin/INR < 1.7
15. Creatinine < 1.5x ULN or creatinine clearance > 60 mL/min
16. Total Bilirubin < 3.0
17. Esophageal varices, if present, must be < Grade 2 and can not have had bleeding in
the last 6 months. If clinically indicated, a standard care Esophageal Gastric
Duodenoscopy (EGD) is recommended to rule out uncontrolled esophageal varices. NOTE:
EGD is not required for enrollment.
18. Documented virology status of hepatitis, as confirmed by HBV / HCV serology test.
Patients with known hepatitis are allowed on this study provided they meet all other
eligibility criteria. Concomittant therapy for hepatitis is permitted at the
principal investigator's discretion.
19. No known history or suspected human immunodeficiency virus (HIV). Note that patients
who are HIV positive are eligible, provided they are under treatment with highly
active antiretroviral therapy (HAART) and have a CD4 count ≥ (350) cells/microliter,
and no known detectable viral load, at the time of study entry. Note also that HIV
testing is not required for eligibility for this protocol.
Exclusion Criteria
1. Hepatocelluar carcinoma (HCC) or other mixed subtype (fibrolamellar HCC, or
sarcomatoid HCC) amenable to curative surgery or transplant
2. Diagnosed with a psychiatric illness or is in a social situation that would limit
compliance with study requirements.
3. Is pregnant or breastfeeding.
4. Prior Abdominal radiation, including prior arterial Yttrium therapy.
5. History of autoimmune disease.
6. Current use of immunosuppressive drugs, such as corticosteroids, or TNF-alpha
blockers.
7. Concurrent active secondary malignancy, excluding indolent cancers such as treated
cutaneous malignancies or treated chronic lymphocytic leukemia, or prior cancers now
in remission for 3 years or longer.
8. Direct tumor extension into the stomach or duodenum. Small bowel or large bowel or
untreated esophageal varices greater than Grade 3 are not allowed.
9. Measureable common or main branch biliary duct involvement with HCC.
10. Severe active co-morbidities
11. All participants: Participants should not donate blood or blood components while
participating in this study and through 180 days after the last study dose.
12. Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8
weeks before first dose of study treatment. Complete wound healing from major
surgery must have occurred 1 month before first dose and from minor surgery (eg,
simple excision, tooth extraction) at least 10 days before first dose. Patients with
clinically relevant ongoing complications from prior surgery are not eligible.
13. History of organ transplantation.
14. Uncontrolled hypertension despite optimal antihypertensive treatment in the opinion
of the principal investigator.
15. Uncontrollable ascites or pleural effusion.
16. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 8 weeks before first dose. Note: Complete healing of an intra-abdominal
abscess must be confirmed before first dose.
17. Active autoimmune disease (active defined as having autoimmune disease related
symptoms and detectable autoantibodies) that has required systemic treatment in the
past 2 years.
18. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or
any other form of immunosuppressive therapy within 7 days prior to the first dose of
study drugs. Except Intranasal, inhaled, topical steroids, or local steroid
injections (e.g., intra articular injection), Systemic corticosteroids at
physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, Steroids
as premedication for hypersensitivity reactions (e.g., CT scan premedication).
19. Clinically significant gross hematuria, hematemesis, or hemoptysis of >0.5 tsp
(2.5ml) of red blood, or other history of grade 3 significant bleeding within 8
weeks.
22. Cholangiocarcinoma (intra/extra-hepatic).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Kansas Medical Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amanda Schroeder, MPH
Phone:
913-588-3600
Email:
aschroeder3@kumc.edu
Contact backup:
Last name:
Maggie Messplay, BS
Phone:
913-588-3610
Email:
smessplay@kumc.edu
Investigator:
Last name:
David Akhavan, MD
Email:
Principal Investigator
Start date:
February 23, 2023
Completion date:
February 28, 2025
Lead sponsor:
Agency:
University of Kansas Medical Center
Agency class:
Other
Collaborator:
Agency:
Varian Medical Systems
Agency class:
Industry
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/NCT05727787
