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New treatment option for Advanced Hepatocellular Carcinoma
Official title Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT04430452
What this study is testing
What is Durvalumab?
Durvalumab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for advanced hepatocellular carcinoma.
Also referred to as Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing). In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 3 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy (e.g., nivolumab and/or pembrolizumab...
- At least 1 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable tumor present which has not received RT or other local therapy prior...
- Clinical indication for RT to any site (e.g. painful primary or metastatic tumor, local complication risk such as impending biliary or vascular...
- Child Pugh score of A, B7, or B8 provided other liver function criteria are met.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
You likely can't join if
- Prior radiotherapy to tumor sites requiring RT which could compromise safety of additional treatments.
- Prior radiotherapy to more than 30% of bone marrow or to a wide field within 4 weeks of the first study treatment.
- Prior treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or PD-L1 inhibitor.
- History of allogenic organ transplantation.
- On prior PD-1 inhibitor immunotherapy:
- Any immune-related adverse events with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 grade \>=...
See the full eligibility criteria
Who can join
- Histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy (e.g., nivolumab and/or pembrolizumab or atezolizumab; prior durvalumab excluded), or without prior PD-(L)1...
- At least 1 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment.
- Clinical indication for RT to any site (e.g. painful primary or metastatic tumor, local complication risk such as impending biliary or vascular obstruction).
- Child Pugh score of A, B7, or B8 provided other liver function criteria are met.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Appropriate antiviral therapy for hepatitis B virus (HBV) according to institutional standard of care with HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) \< 2000 IU/mL.
- Adequate organ function as defined below:
- Hemoglobin \>= 9.0 g/dL
- Absolute neutrophil count \>= 1,200/microliter (mcL)
- Platelet count \>= 60,000/mcL
- Serum bilirubin =\< 1.5 x institutional upper limit of normal. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the...
- Aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case it can be =\< 5 x upper limit of normal (ULN)
- International normalized ratio (INR) \< 1.5
- Creatinine clearance \> 30 mL/min by Cockcroft Gault formula.
- No contraindication to immune checkpoint inhibitor immunotherapy.
- No contraindication to RT.
- Age \>=18 years at time of study entry.
- Life expectancy of \>= 12 weeks.
- Body weight \> 30 kg (66.1 pounds).
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an...
- Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and...
- Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last...
- Women of childbearing potential and men must agree to use adequate contraception from the time of screening through the duration of study participation and for at least 6 months after receiving combination of durvalumab...
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally...
What rules you out
- Prior radiotherapy to tumor sites requiring RT which could compromise safety of additional treatments.
- Prior radiotherapy to more than 30% of bone marrow or to a wide field within 4 weeks of the first study treatment.
- Prior treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or PD-L1 inhibitor.
- History of allogenic organ transplantation.
- On prior PD-1 inhibitor immunotherapy:
- Any immune-related adverse events with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 grade \>= 3 on any prior immunotherapy or toxicity that led to permanent...
- Any AEs while receiving prior immunotherapy not resolved to grade =\< 1 or resolved to baseline, with the exception of patients with endocrine AE of grade =\< 2, who are permitted to enroll if they are stably maintained...
- Required the use of additional immunosuppression other than corticosteroids for the management of an AE, experienced recurrence of a grade \>= 3 AE if previously re-challenged, and currently require maintenance doses of...
- Major surgery, liver-directed therapy, or any other anticancer therapy (e.g. chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) less than 4...
- Any other unresolved toxicity NCI CTCAE grade \>= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician
- Concurrent enrollment in another treatment clinical study, except only in the follow-up period of that study.
- Participation in another treatment clinical study with an investigational product during the past 4 weeks except only in the follow-up period of that study.
- 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...
- 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 study physician
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial...
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease \>= 2 years before the first dose of investigational product (IP) and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis.
- History of active primary immunodeficiency.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice).
- Known human immunodeficiency virus (HIV) infection.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab/tremelimumab. 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 not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening through the duration of study participation and...
- Known allergy or hypersensitivity to IP, any of the study drugs, or any of the study drug excipients.
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
The study team makes the final eligibility decision.
Where it's taking place
- San Francisco, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 3 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include San Francisco, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.