TriangleNCT01908426 · CITED IN SOURCE DOCUMENTS
Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2021-05-06
The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with placebo on overall survival in subjects with advanced hepatocellular carcinoma who have received prior sorafenib.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Who could take part
- eligibility Criteria
- Select Inclusion Criteria: 1. Histological or cytological diagnosis of HCC. 2. The subject has disease that is not amenable to a curative treatment approach. 3. Received prior sorafenib. 4. Progression following at least 1 prior systemic treatment for HCC. 5. Recovery to from toxicities related to any prior treatments. 6. ECOG performance status of 0 or 1. 7. Adequate hematologic and renal function, based upon meeting protocol defined laboratory criteria within 7 days before randomization. 8. Child-Pugh Score of A. 9. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection. 10. Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment. 11. Female subjects of childbearing potential must not be pregnant at screening. Select Exclusion Criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma. 2. Receipt of more than 2 prior systemic therapies for advanced HCC. 3. Any type of anticancer agent (including investigational) within 2 weeks before randomization. 4. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment within 6 weeks of randomization. 5. Prior cabozantinib treatment. 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization. 7. Concomitant anticoagulation, at therapeutic doses, with anticoagulants. 8. Serious illness other than cancer that would preclude safe participation in the study. 9. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. 10. Moderate or severe ascites. 11. Pregnant or lactating females. 12. Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Cabozantinib (XL184) 60 mg tablet once daily
- intervention Names
- Drug: Cabozantinib tablets
- label
- Cabozantinib (XL184)
- type
- EXPERIMENTAL
- description
- Oral cabozantinib-matched placebo tablet once daily
- intervention Names
- Drug: Placebo tablets
- label
- Placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Cabozantinib (XL184)
- name
- Cabozantinib tablets
- other Names
- XL184
- type
- DRUG
- arm Group Labels
- Placebo
- name
- Placebo tablets
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 707
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- The primary analysis of OS is defined as the time from randomization to death from any cause. The analysis was based on a second planned interim analysis prespecified to be performed at approximately the 75% information fraction (ie, at approximately 466 deaths). The data cutoff date for this event-driven analysis in the Intent to Treat (ITT) population was 01 June 2017. Median OS was calculated using the Kaplan-Meier estimates.
- measure
- Overall Survival (OS)
- time Frame
- Up to 45 months
- secondary Outcomes
- description
- Duration of PFS is defined as the time of randomization to the earlier of the following events, progressive disease as determined by Investigator (per RECIST 1.0, which is defined by a ≥ 20% increase in the sum of the longest diameter of target lesions from baseline) or death due to any cause. A Kaplan- Meier analysis was performed to estimate the median duration.
- measure
- Progression-Free Survival (PFS)
- time Frame
- Up to 45 months
- description
- Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- measure
- Objective Response Rate (ORR)
- time Frame
- ORR is measured by radiologic assessment every 8 weeks after randomization until disease progression or discontinuation of study treatment (up to 45 months)
Full study description
- brief Summary
- The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with placebo on overall survival in subjects with advanced hepatocellular carcinoma who have received prior sorafenib.
Source references
- references
- citation
- Freemantle N, Mollon P, Meyer T, Cheng AL, El-Khoueiry AB, Kelley RK, Baron AD, Benzaghou F, Mangeshkar M, Abou-Alfa GK. Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial. Eur J Cancer. 2022 Jun;168:91-98. doi: 10.1016/j.ejca.2022.03.021. Epub 2022 Apr 26.
- pmid
- 35487183
- type
- DERIVED
- citation
- El-Khoueiry AB, Meyer T, Cheng AL, Rimassa L, Sen S, Milwee S, Kelley RK, Abou-Alfa GK. Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial. BMC Cancer. 2022 Apr 9;22(1):377. doi: 10.1186/s12885-022-09453-z.
- pmid
- 35397508
- type
- DERIVED
- citation
- Kelley RK, Miksad R, Cicin I, Chen Y, Klumpen HJ, Kim S, Lin ZZ, Youkstetter J, Hazra S, Sen S, Cheng AL, El-Khoueiry AB, Meyer T, Abou-Alfa GK. Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade. Br J Cancer. 2022 Mar;126(4):569-575. doi: 10.1038/s41416-021-01532-5. Epub 2021 Oct 7.
- pmid
- 34621044
- type
- DERIVED
- citation
- Trojan J, Mollon P, Daniele B, Marteau F, Martin L, Li Y, Xu Q, Piscaglia F, Zaucha R, Sarker D, Lim HY, Venerito M. Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein >/= 400 ng/mL: A Matching-Adjusted Indirect Comparison. Adv Ther. 2021 May;38(5):2472-2490. doi: 10.1007/s12325-021-01700-2. Epub 2021 Apr 6.
- pmid
- 33822328
- type
- DERIVED
- citation
- Kelley RK, Ryoo BY, Merle P, Park JW, Bolondi L, Chan SL, Lim HY, Baron AD, Parnis F, Knox J, Cattan S, Yau T, Lougheed JC, Milwee S, El-Khoueiry AB, Cheng AL, Meyer T, Abou-Alfa GK. Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial. ESMO Open. 2020 Aug;5(4):e000714. doi: 10.1136/esmoopen-2020-000714.
- pmid
- 32847838
- type
- DERIVED
- citation
- Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klumpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. doi: 10.1056/NEJMoa1717002.
- pmid
- 29972759
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice