Trial Title:
SIRT With Tremelimumab and Durvalumab for Resectable HCC
NCT ID:
NCT05701488
Condition:
Resectable Hepatocellular Carcinoma
Hepatocellular Carcinoma
Hepatocellular Cancer
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Durvalumab
Tremelimumab
Conditions: Keywords:
Resectable Hepatocellular Carcinoma
Hepatocellular Carcinoma
Hepatocellular Cancer
Liver Cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
Intravenous infusion
Arm group label:
Durvalumab + Tremelimumab (Arm A)
Arm group label:
Durvalumab + Tremelimumab + SIRT (Arm B)
Other name:
Imjudo
Other name:
MEDI4736
Intervention type:
Drug
Intervention name:
Tremelimumab
Description:
Intravenous infusion
Arm group label:
Durvalumab + Tremelimumab (Arm A)
Arm group label:
Durvalumab + Tremelimumab + SIRT (Arm B)
Other name:
Imfinzi
Intervention type:
Device
Intervention name:
SIRT
Description:
SIR (Selective Internal Radiation) Sphere resin microspheres, radioactive particles
delivered via injection into an artery.
Arm group label:
Durvalumab + Tremelimumab + SIRT (Arm B)
Other name:
Selective Internal Yttrium-90 Radioembolization
Summary:
The goal of this research study is to evaluate the safety and tolerability of
tremelimumab and durvalumab with or without Selective Internal Yttrium-90
Radioembolization (SIRT) in participants with resectable hepatocellular carcinoma (HCC)
who will undergo liver surgery.
The names of the interventions involved in this study are:
- Durvalumab (a type of immunotherapy)
- Tremelimumab (a type of immunotherapy)
- Selective Internal Yttrium-90 Radioembolization (SIRT) (a type of radiation
microsphere bead)
Detailed description:
This is a Phase 1, open-label, randomized research study to evaluate the safety and
tolerability of tremelimumab and durvalumab with or without Selective Internal Yttrium-90
Radioembolization (SIRT) in participants with resectable hepatocellular carcinoma (HCC)
who will undergo liver surgery.
Participants will be randomized into one of two treatment groups: Durvalumab +
Tremelimumab versus Durvalumab + Tremelimumab + SIRT. Randomization means that a
participant is put into a group by chance. Radioembolization is a combination of
radiation therapy and a procedure called embolization to treat cancer. SIRT blocks tumor
blood supply by injecting radioactive particles into the hepatic artery and delivers
internal radiotherapy on the tumor.
The U.S. Food and Drug Administration (FDA) has not approved Durvalumab as treatment for
HCC but it has been approved for other uses.
The U.S. FDA has not approved tremelimumab as a treatment option for HCC.
The research study procedures include screening for eligibility, study treatment
including evaluations, radiology scans of the liver, blood tests, electrocardiograms, and
follow up visits.
Participation in this study is expected to last about 18 months with long-term follow up
for a maximum of 3 years.
It is expected that about 20 people will take part in this research study.
AstraZeneca, a pharmaceutical company, is supplying the study drugs, tremelimumab and
durvalumab. Sirtex Medical Inc., a medical device company, is supplying the Yttrium-90
resin Microsphere beads.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically confirmed HCC (documentation of original biopsy for diagnosis is
acceptable if tumor tissue is unavailable) or clinical diagnosis by American
Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects
(presence of arterial hypervascularity with venous washout). For subjects without
cirrhosis, histological confirmation is mandatory.
- Participants must have resectable disease. Those patients must have preserved liver
function (Child A) and with either AJCC stage IA, IB, II, and IIIA or BCLC stage 0
or stage A disease. The determination of resectability will ultimately lie in the
clinical judgment of the treating investigator and surgical oncologist involved in
the care of the patient.
- Participants must be treatment naïve for HCC.
- Age ≥18 years. Because no dosing or adverse event data are currently available on
the use of tremelimumab, durvalumab, and SIRT in participants <18 years of age,
children are excluded from this study.
- Measurable disease per RECIST 1.1 criteria.
- ECOG performance status ≤ 1 (see Appendix A).
- Body weight >30 kg.
- Participants must have adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute Neutrophil Count (ANC) ≥ 1,000 /mcL
- Platelets ≥ 80,000 /mcL
- Total Bilirubin ≤ 2.0 mg/dL
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN)
- Measured Creatinine Clearance > 40 mL/min by 24-hour urine collection, or
- Calculated Creatinine Clearance (CL) > 40 mL/min by the Cockcroft-Gault Formula
(Cockcroft Gault 1976):
- Males: Creatinine CL (mL/min) = (weight (kg) × (140 - Age)) / (72 × serum
creatinine (mg/dL))
- Females: Creatinine CL (mL/min) = (weight (kg) × (140 - Age) / (72 × serum
creatinine (mg/dL))) × 0.85
- Women of childbearing potential (WOCBP, refer to Section 5.4) must have a negative
serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of
human chorionic gonadotropin [HCG]) obtained during the trial screening period.
- Men and WOCBP must agree to follow the protocol instructions for acceptable
method(s) of contraception for the duration of trial treatment and for a total of 5
months post-treatment completion. Refer to Section 5.4.
- Participants with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen as assessed by the treating investigator
are eligible for this trial.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Participants who have received any prior treatment for HCC.
- Patients who have had a major surgical procedure, open biopsy, or significant
traumatic injury with poorly healed wound within 6 weeks prior to first dose of
study drug.
- History of allogenic organ transplantation.
- Participants who are receiving any other investigational agents.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to
this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients with celiac disease controlled by diet alone
- Patients without active disease in the last 5 years may be included but only
after consultation with the sponsor-investigator
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to durvalumab or tremelimumab.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection (including tuberculosis), uncontrolled hypertension (defined as blood
pressure of > 140/90 mmHg during the screening period despite medical management),
interstitial lung disease, serious chronic gastrointestinal conditions associated
with diarrhea, or psychiatric illness/social situations that would limit compliance
with study requirement, substantially increase risk of incurring AEs, or compromise
the ability of the patient to give written informed consent.
- Patients who have a primary brain tumor (excluding meningiomas and other benign
lesions), any brain metastases, leptomeningeal disease, seizure disorders not
controlled with standard medical therapy, or history of a stroke within the year
prior to the first dose of study drug.
- History of active primary immunodeficiency.
- Known active infection of human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)
--Patients positive for HIV are allowed on study, but HIV-positive patients must
have:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the
prevention of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load or standard
PCR-based tests
- Known active hepatitis B infection (known positive HBV surface antigen (HBsAg)
result). Patients with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
- Known active hepatitis C infection. Participants positive for hepatitis C (HCV)
antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of study agent. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular injection)
- Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
drug. Note: Patients, if enrolled, should not receive live vaccine whilst receiving
study drug and for at least 30 days after the last dose of study agent.
- History of serious systemic disease, including myocardial infarction or unstable
angina within the 12 months prior to the first dose of study drug, history of
hypertensive crisis or hypertensive encephalopathy, New York Heart Association
(NYHA) grade II or greater congestive heart failure, unstable symptomatic arrhythmia
requiring medication (patients with chronic atrial arrhythmia, i.e., atrial
fibrillation or paroxysmal supraventricular tachycardia are eligible), significant
vascular disease or symptomatic peripheral vascular disease.
- Participants who have a known clinical history of coagulopathy, bleeding diathesis,
or thrombosis within the 12 months prior to the first dose of study drug.
- Participants who have a serious, non-healing wound, ulcer, bone fracture or with
history of pneumonitis or interstitial lung disease.
- Participants who are pregnant or breastfeeding. A negative serum or urine pregnancy
test obtained during the screening period is required for trial enrollment.
- Participants requiring total parenteral nutrition with lipids.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jiping Wang, MD, PhD
Phone:
617-732-8910
Email:
jwang39@partners.org
Start date:
April 21, 2023
Completion date:
October 1, 2025
Lead sponsor:
Agency:
Jiping Wang, MD, PhD
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Sirtex Medical
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05701488
