Trial Title:
Clinical Investigation Evaluating Safety and Efficacy of Selective Intra-arterial 166Holmium Radiation Therapy in Combination With Atezolizumab and Bevacizumab for Non Resectable Hepatocellular Carcinoma
NCT ID:
NCT05705791
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Study type:
Interventional
Study phase:
N/A
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Simon's two stage design: In the first stage, 23 evaluable patients will be accrued. If
there are 7 or fewer responses (complete or partial response) in these 23 patients, the
clinical investigation will be stopped for futility. Otherwise, 10 additional evaluable
patients will be accrued for a total of 33.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
QuiremSpheres
Description:
166Holmium selective internal intra-arterial radiation therapy at C1D15 of the
Atezolizumab and Bevacizumab therapy
Arm group label:
166Holmium SIRT arm
Other name:
166Holmium microspheres
Other name:
166Holmium SIRT
Summary:
The goal of this clinical trial is to evaluate the added value of 166Holmium SIRT to
Atezolizumab-Bevacizumab in patients with non resectable HCC. The primary endpoint is the
Best Objective Response Rate at 6 months after 166Holmium SIRT according to mRECIST.
Participants will be treated by :
- Approved first line systemic therapy: Atezolizumab (1200mg Q3W, IV) with Bevacizumab
(15mg/kg Q3W, IV)
- In combination with 166Holmium selective internal intra-arterial radiation therapy
(Quirem Spheres®, the investigational medical device) after a work-up phase
considered as "favorable".
Participants will be followed up to 12 months after the first cycle of Atezolizumab and
Bevacizumab therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Men and women ≥ 18 years old
- Patient should understand, sign, and date the written informed consent form prior to
any investigation-specific procedures performed.
- Patient should be able to comply with investigational procedure, tissue and blood
sample collection and willing to comply with investigation visits and procedures as
per clinical investigation plan.
- Patients must have pathological confirmation of HCC.
- HCC classed Barcelona Clinic Liver Cancer (BCLC) stage C
- Patient should be considered as non resectable by Multidisciplinary Team and liver
surgeon, and non-eligible for liver transplantation
- Patient should be eligible for 1st line Atezolizumab and Bevacizumab combination
therapy. Patients previously treated by a local therapy are eligible.
- Patient with active intrahepatic HCC.
- Patients with or without active viral infection (i.e., HCV, HBV) are eligible. In
case of active hepatitis B, the patient should be treated with an anti-HBV therapy
during the investigational procedure.
- Patients should have measurable disease as defined by mRECIST criteria for response
assessment.
- ECOG status of 0 or 1 (Appendix 2).
- Life expectancy of ≥ 12 weeks at the time of informed consent per Investigator
assessment.
- Adequate organ function as defined by the following:
1. White blood cells (WBCs) ≥ 2000/mL
2. Platelets ≥ 70 × 103/mL
3. Hemoglobin ≥ 8.0 g/dL
4. Creatinine < 1.5 × ULN or creatinine clearance ≥ 40mL/min (Cockcroft-Gault
formula)
5. ALT and AST ≤ 3 × ULN
6. Lipase and amylase ≤ 1.5 × ULN
7. Total bilirubin ≤ 1.5 × ULN
- Child-Pugh A, Without history of encephalopathy or clinically significant ascites
- Women of childbearing potential (WOCBP) must have a negative urine or serum β-HCG
pregnancy test within 7 days prior registration. If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required. Sexually
active female patients must agree to use two methods of effective contraception*,
one of them being a barrier method, or to abstain from sexual activity during the
clinical investigation and for at least 6 months after last drug administration of
the investigational procedure or must refrain from heterosexual activity during this
same period**.
* Acceptable contraceptive methods include single or combined contraceptive methods
that result in a failure rate of < 1% per year, such as: tubal ligation, male
sterilization, hormonal implants, proper use of combined oral or injected hormonal
methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of < 1% per year. Barrier methods must always be
supplemented with the use of a spermicide.
** Abstinence is acceptable only if it is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable methods
of contraception.
- Sexually active males patients must agree to use condom during the clinical
investigation and for at least 7 months after the last drug administration of the
investigational procedure. Also, it is recommended the childbearing potential female
partner uses a highly effective method of contraception for the same duration.
- Patients shall be eligible to undergo pre-treatment and on-treatment tumor biopsies.
Patients who either do not consent to a pre-treatment tumor biopsy or do not have
accessible lesions will not be eligible.
- Patients must be affiliated to a social security system or beneficiary of the same
Exclusion Criteria:
- Patients with a prior malignancy are excluded, except those with prior malignancies
treated more than 2 years previously (at the time of informed consent) with curative
intent with no evidence of disease during the interval and who are considered by the
Investigator to present a low risk for recurrence, will be eligible.
- A known or underlying medical condition that, in the opinion of the Investigator,
could make the administration of investigational procedure combination hazardous to
the subject or could adversely affect the ability of the subject to comply with or
tolerate clinical investigation.
- Requirement for daily supplemental oxygen
- Previous external radiation therapy to the liver
- Uncorrectable abnormal vascular anatomy at pre-assessment angiogram that would
result in significant reflux to of hepatic arterial blood to the lung, stomach,
pancreas or bowel
- Complete main portal vein thrombosis
- History or active autoimmune disease with the following exceptions: patients with a
history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement
hormone, patients with controlled Type 1 diabetes mellitus on a stable insulin
regimen and patients with mild autoimmune skin disorders (such as eczema or atopic
dermatitis involving <10% of the skin) may be eligible for this clinical
investigation
- Any of the following within the 6 months prior to clinical investigation entry:
myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
attack.
- A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the
year prior to informed consent.
- Positive blood screen for human immunodeficiency virus (HIV) with acquired
immunodeficiency syndrome (AIDS). Patients with controlled HIV infection under
anti-retroviral therapy and normal CD4+ T-cell counts (>500/mm3) could be considered
eligible by the investigator if the patient fulfills the other inclusion/exclusion
criteria.
- Evidence of active infection that requires systemic antibacterial, antiviral, or
antifungal therapy ≤ 7 days prior to inclusion.
- Any other significant acute or chronic medical illness. Any other sound medical,
psychiatric, and/or social reason as determined by the Investigator.
- Subjects who are unable to undergo and/or tolerate venous AND arterial access
(evaluated on pre-treatment imaging)
- Patients that have received within 4 weeks or 5 half-lives (whichever is shorter)
from inclusion and who are planned to receive the following during investigational
procedure:
- Any other investigational drug
- Any anticancer therapy (chemotherapy, biologics, therapeutic vaccines,
radiotherapy, or hormonal treatment).
- Treatment with capecitabine within two months prior to treatment, or patient
who will be treated with capecitabine at any time following treatment with
QuiremSpheres®
- Concomitant use of herbal therapies/traditional Chinese medicine with
anti-cancer activity included in the label is not permitted because of
potential drug-drug interactions.
- Vaccines containing replicating live virus
- Allergen hyposensitization therapy
- Growth factors, e.g., granulocyte-colony stimulating factor (G-CSF),
granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin
- Major surgery. The patient must recover from any major surgical operations
before being treated with QuiremSpheres.
- Bisphosphonates or anti-RANKL therapy
- Systemic corticosteroids or other systemic immunosuppressive medications. The
use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
is allowed.
- Coumadin or warfarin are prohibited. The use of LMWH is allowed.
- Local treatments on the targeted tumors (percutaneous ablations,
chemoembolization, radiation therapy, or liver surgery).
- Previous allogeneic hematopoietic stem cell transplantation or previous solid organ
transplantation requiring systemic immunosuppressive therapy
- History of severe allergy, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies or to biopharmaceutical produced in Chinese hamster
ovarian cells or to any components of the drugs of the investigational procedure
- Patient under guardianship or deprived of his liberty by a judicial or
administrative decision or incapable of giving its consent
- Pregnant or breastfeeding women or intending to become pregnant during the clinical
investigation.
- Patients with untreated or incompletely treated varices with bleeding or high-risk
for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all
size of varices (small to large) must be assessed and treated per local standard of
care prior to enrollment. Patients who have undergone an EGD within 6 months of
prior to initiation of investigational procedure (D1C1 of the
Atezolizumab/Bevacizumab therapy) do not need to repeat the procedure.
- Inadequately controlled arterial hypertension (defined as systolic blood pressure
(BP) > or = 150 mmHg and/or diastolic blood pressure > 100 mmHg), based on an
average of > or = 3 BP readings on > or = 2 sessions
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to initiation of
investigational procedure (D1C1 of the Atezolizumab/Bevacizumab therapy)
- History of hemoptysis (> or = 2.5 mL of bright red blood per episode) within 1 month
prior to initiation of investigational procedure (D1C1 of the
Atezolizumab/Bevacizumab therapy)
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)
- Any other contraindication to the experimental medical device use :
- ascites or are in clinical liver failure;
- significantly abnormal synthetic and excretory liver function tests (LFTs);
- a lung dose exceeding 30 Gy in a single treatment;
- uncorrectable extrahepatic deposition. Activity in the falciform ligament,
portal lymph nodes and gallbladder is accepted.
- History of hypersensitivity reactions to the active substance of 99mTc-MAA or to one
of its excipients or to one of the components of the radiolabeled pharmaceutical.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
AP-HP Hôpital Beaujon
Address:
City:
Clichy
Zip:
92110
Country:
France
Facility:
Name:
Centre Georges-François Leclerc
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
CHU François Mitterand
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
Hôpital Saint Eloi
Address:
City:
Montpellier
Zip:
34000
Country:
France
Facility:
Name:
CHU Nantes
Address:
City:
Nantes
Zip:
44000
Country:
France
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94800
Country:
France
Start date:
February 7, 2023
Completion date:
August 2026
Lead sponsor:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Source:
Gustave Roussy, Cancer Campus, Grand Paris
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05705791
