Clinical trial NCT03298451: Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Official title: A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma Non-Resectable
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-10-02
Enrollment: 1324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy

Detailed description: The study population includes patients 18 years of age or older with advanced HCC, Barcelona Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh A classification liver disease. Patients must not have received any prior systemic therapy for unresectable HCC.

Patients in all treatment arms may continue receiving their originally assigned treatment, at the Investigator's discretion, until progression

Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to receive benefit from their assigned treatment and meet the criteria for treatment in the setting of PD may continue to receive their assigned treatment.

If a patient discontinues study drug(s) due to disease progression, the patient will enter survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic deterioration or who have commenced subsequent anticancer therapy, will have tumor assessments until confirmed PD and will be followed for survival

Eligibility criteria: Inclusion criteria

* HCC based on histopathological confirmation
* No prior systemic therapy for HCC
* Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
* Child-Pugh Score class A
* ECOG performance status of 0 or 1 at enrollment

Exclusion criteria

* Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy
* Clinically meaningful ascites
* Main portal vein tumor thrombosis
* Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
* HBV and HVC co-infection, or HBV and Hep D co-infection

Primary outcomes:
measure: Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg
timeFrame: From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
Secondary outcomes:
measure: Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg
timeFrame: From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
measure: Overall Survival (OS) at 18, 24, and 36 Months After Randomization
timeFrame: At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).
measure: Progression Free Survival (PFS)
timeFrame: Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)
measure: Time To Progression (TTP)
timeFrame: From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: Objective Response Rate (ORR)
timeFrame: From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: Disease Control Rate (DCR)
timeFrame: From the date of randomization until objective tumor progression or date of death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: Duration of Objective Response (DoR)
timeFrame: From the date of first documented response until the first date of documented progression or death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: Overall Survival (OS) by PD-L1
timeFrame: From the date of randomization until death due to any cause, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration
timeFrame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
measure: EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration
timeFrame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
measure: EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration
timeFrame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
measure: EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration
timeFrame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
measure: Presence of ADA for Durvalumab
timeFrame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of durvalumab. Assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
measure: Presence of ADA for Tremelimumab
timeFrame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of tremelimumab. Assessed up to approximately 46 months after the first randomization.
measure: Summary of Durvalumab Concentration Over Time
timeFrame: To evaluate the PK of Durvalumab, samples were collected pre-dose at week 4 and week 12 and post-dose at week 12. Assessed at the final analysis DCO (27Aug2021).
measure: Summary of Tremelimumab Concentration Over Time
timeFrame: To evaluate the PK of Tremelimumab, samples were collected at week 0 (post-dose), week 4, and week 12. Assessed at the final analysis DCO (27Aug2021).
Other outcomes:
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state: Gyeonggi-do
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city: Uzhgorod
country: Ukraine
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city: Hanoi
country: Vietnam
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city: Hochiminh
country: Vietnam
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Study officials:
References: