Hepatocellular CarcinomaPhase 2NCT05048017
Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma
A Phase 2 study testing Regorafenib and PD-1 inhibitor in people with Hepatocellular Carcinoma and Regorafenib, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
This is a single arm, nonrandomized, single center clinical study to investigate the safety and efficacy of regorafenib combined with PD-1 inhibitor therapy for second-line treatment of hepatocellular carcinoma Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Regorafenib, PD-1 Inhibitor
- What is being tested?
- Regorafenib and PD-1 inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2021to 1 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must meet all of the following criteria to be enrolled in the study:
- Subjects volunteer to participate in the study, agree to sign their written informed consent, show good compliance and are cooperative with the follow-up.
- There is no gender requirement but age requirement (age>18) for the subjects who sign the informed consent.
- The subjects were diagnosed as advanced hepatocellular carcinoma (HCC) by imaging or histological examination.
- The disease is not suitable for radical surgery and/or local treatment, or disease progression occurs after surgery and/or local treatment.
- The patients with at least one measurable lesion according to RECIST, version1.1, and no local radiotherapy was performed. Results of spiral CT scan (RECIST, version 1.1): LD (lesion) ≥ 10 mm or SD (enlarged lymph node) ≥ 15 mm.
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- The patients who failed or were intolerable to the following treatments: simple sorafenib therapy, or sorafenib combined with PD-1 therapy, or simple lenvatinib therapy, or lenvatinib combined with PD-1 therapy, or bevacizumab combined with atezolizumab.
- Definition of treatment failure: It refers to the disease progression during treatment or the recurrence of the disease after treatment (Obvious disease recurrences and progressions appeared in patients who have received at least one radical or palliative resection, interventional therapy or radiotherapy. The treatment period of systemic chemotherapy like oxaliplatin and other systemic chemotherapy must be at least one cycle. The treatment time of molecular targeted therapy must be longer than 14 days).
- Definition of intolerable: Hematological toxicity ≥ Grade IV, or non-hematological toxicity ≥ Grade III, or damage to the heart, liver, kidney and other major organs ≥ Grade II occurred during the treatment. For details, please refer to the package inserts of each drug.
- The ECOG score within 1 week before enrollment was 0-1 points.
- Child-Pugh score for liver function: Class A, BCLC staging is B-C stage.
- The time from failure of first-line system treatment to enrollment in this study (the time to sign the informed consent form) was ≥ 2 weeks , and the adverse events basically returned to normal (NCI-CTCAE ≤ Grade I).
- The expected survival time is greater than or equal to 6 months.
- HBV DNA < 2000 IU/ml (104 copies/ml).
- Hematology and organ function are adequate, based on the following laboratory test results obtained within 14 days prior to the start of study treatment (unless otherwise stated):
- 14.1 Routine blood test: (No blood transfusion, G-CSF treatment, or medication correction within 14 days prior to screening) 14.2 Hb ≥ 100 g/L; Neutrophils ≥ 1.5 × 109/L; PLT ≥ 75 × 109/L 14.3 Biochemical examination: (No ALB was administered within 14 days) ALB ≥ 35 g/L; ALT and AST<3×ULN; TBIL ≤ 2×ULN; Creatinine ≤ 1.5×ULN; PT ≤ ULN+4S; INR ≤ 2.2 (In the Child-Pugh score, only one of albumin and bilirubin can be scored as 2 points)
- No active autoimmune disease requiring systemic treatment in the past 2 years (i.e. using disease modulators, corticosteroids, or immunosuppressive agents). Alternative therapy (e.g., physiological corticosteroid replacement therapy for thyroxine, insulin, or adrenal or pituitary insufficiency, etc.) is not considered as a form of systemic therapy.
- Reproductive women: Agree to abstain from sex (avoid heterosexual intercourse) or use a contraceptive method with an annual contraceptive failure rate < 1% during treatment and for at least 6 months after the last administration.
- 16.1 If the female patient has menstruation and has not yet reached the post-menopausal state (continuous non-menstrual period ≥ 12 months, with no other reasons other than menopause are found), and have not undergone sterilization (removal of the ovaries and/or uterus), it is considered that the patient is fertile.
- 16.2 Examples of contraceptive methods with an annual contraceptive failure rate < 1% include bilateral fallopian tube ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper-ring intrauterine devices.
- 16.3 The reliability of sexual control should be evaluated relative to the duration of the clinical trial and the preferred and daily lifestyle of the patient. Periodic abstinence (for example, calendar days, ovulatory period, symptomatic body temperature, or post-ovulation methods) and external ejaculation are unacceptable methods of contraception.
- Male: Agree to abstinence (not having heterosexual intercourse) or use contraceptive measures, and agree not to donate sperm, defined as follows:
- 17.1 When his female partner has fertility, the male patient must abstain from sex during treatment and within 6 months after the last administration, or use condoms and other contraceptive methods to make the annual contraceptive failure rate < 1%. Male patients must agree not to donate sperm during the same time period. When his female partner is pregnant, the male patient must abstain from sex or use a condom for contraception during the treatment period and within 6 months after the last dose to avoid the fetus being affected by the study.
- The reliability of sexual control should be evaluated relative to the duration of the clinical trial and the preferred and daily lifestyle of the patient. Periodic abstinence (for example, calendar days, ovulatory period, symptomatic body temperature, or post-ovulation methods) and external ejaculation are unacceptable methods of contraception.
- Before the first dose of study medication for biomarker analysis, archived tumor tissue or new tissue biopsy specimens must be available. In the case when the archived tissue cannot be provided, and the biopsy cannot be performed, participants can consult the investigator and join the group after obtaining the investigator's consent.
- Note: If an unstained section is submitted, the new section should be submitted to the testing laboratory within 14 days after cutting.
Who cannot join
- Patients meeting one or more of the following conditions cannot be included:
- The clinical stage is stage IV, and/or patients with hepatobiliary solid tumors with any of the following conditions:
- 1.1 The patient is suitable for surgical radical treatment, 1.2 or, the patient has accepted radical treatment and has no assessable lesion, 1.3 or, the patient has a history of liver transplantation or plans to undergo liver transplantation.
- Patient who is known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components; Patient who is known to be allergic to regorafenib and its components.
- ECOG score ≥ 2 points.
- Patient who has ascites with clinical symptoms, that requires therapeutic abdominal puncture or drainage, or Child-Pugh score > 2 points.
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- Patient with serious heart, cerebrovascular and other systemic diseases with unstable or uncontrollable condition.
- Patient with active central nervous system (CNS) metastasis and/or cancerous meningitis. Subjects with previously treated brain metastases can participate in the study, as long as their brain metastases are stable (imaging shows no evidence of progression for at least four weeks before the first trial treatment and all neurological symptoms have returned to baseline) with no evidence shows new or enlarged brain metastases, and steroids are not used for at least 7 days before the trial treatment. This exception does not include cancerous meningitis, which is excluded regardless of how its clinical stability is.
- Patient who has accepted major surgery within 4 weeks before the first study administration (appropriate wound healing and clinical evaluation must be performed after major surgery, which has nothing to do with the time of enrollment)
- Patient with liver and kidney dysfunction, such as jaundice, ascites, and/or bilirubin > 2×ULN, and/or alkaline phosphatase ≥ 3×ULN; and/or ≥ Grade 3 (CTC-AE 5.0) persistent proteinuria, creatinine ratio > 3.5g/24 hours, or renal failure requiring blood or peritoneal dialysis, etc.
- Urine routine test shows urine protein ≥ ++ or confirmed 24-hour urine protein quantification>1.0g;
- Patient with persistent infection which is greater than Grade 2 (CTC-AE5.0).
- Patient with a history of organ allogeneic transplantation (participants underwent allogeneic tissue/solid organ transplantation)
- Patient with a history of active tuberculosis (TB bacilli)
- Patient intolerance to any study drug (or any excipient)
- Female patient who is pregnant, breastfeeding, or who does not accept contraceptive measures.
- Patient with known or untreated brain metastases, or with epilepsy which needs medication.
- Patient with bone metastases who have received palliative radiotherapy (radiotherapy area > 5% bone marrow area) within 4 weeks before participating in the study, or patient who has unhealed wounds, ulcers or fractures, or has a history of organ transplantation.
- Patient with a history of gastrointestinal bleeding or a clear gastrointestinal bleeding tendency within the past 6 months, such as: esophageal varices with bleeding risk, local active ulcer lesions and fecal occult blood ≥ (++). Gastroscopy is needed for patients with stool occult blood (+);
- There is evidence or history of bleeding mechanism disorders such as bleeding events ≥ Grade 3 (CTC-AE5.0).
- Patient with a history of human immunodeficiency virus (HIV) infection.
- Patient who tests positive for hepatitis B or C and has not received regular treatment.
- Patient with severe non-healing wounds, ulcers or fractures
- Patient treated with regorafenib beforehand.
- Patient diagnosed of immunodeficiency or received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment. After consultation with the sponsor, the use of physiological doses of corticosteroids (not exceeding 7.5 mg/d prednisone or equivalent doses of similar drugs) can be approved.
- Existence of drug abuse; or any medical, psychological or social condition that may affect the research and patient compliance, or even endanger patient safety.
- There are many factors that affect oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction, and conditions which significantly affect the administration and absorption of drugs).
- There is unresolved toxicity > Grade 1 caused by any previous treatment/manipulation (CTC-AE5.0, except for hair loss, anemia, and hypothyroidism).
- Patient who received live virus vaccine within 30 days of the planned start of treatment. Seasonal influenza vaccine without live virus is allowed.
- Patients with objective evidence showing pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired lung function, etc. in the past and at present.
- Patient who received strong CYP3A4 inhibitor treatment within 7 days before participating in the study, or received strong CYP3A4 inducer treatment within 12 days before participating in the study.
- Patient who is participating in another clinical study at the same time.
- Patient who was considered to be unsuitable to participate in this study after the investigator comprehensively judged the condition.
- Termination criteria:
- The subject withdraws the informed consent and asks to withdraw.
- Medical imaging examination confirms the progression of disease, and the treatment is not beneficial for disease progression through clinical judgment.
- After dose adjustment, the subject still cannot tolerate toxicity.
- Other conditions that the investigator considers necessary for the subject to withdraw from the study.
- The sponsor terminates the study due to security concerns.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hai-Tao Zhao
Beijing, Beijing Municipality, 100730
Xiaobo Yang, PhD, 010-69156043, yangxulcyx@163.com
Haitao Zhao, PhD, +861069156042, zhaoht@pumch.cn
About this study
Official title: Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma: A Single Arm, Nonrandomized, Single Center Clinical Study
This is a single arm, nonrandomized, single center clinical study to investigate the safety and efficacy of regorafenib combined with PD-1 inhibitor therapy for second-line treatment of hepatocellular carcinoma
Read the detailed description
To observe and evaluate the efficacy, safety and biomarker analysis of regorafenib combined with PD-1 inhibitor for the second-line treatment of hepatocellular carcinoma.In this study, 20 patients with hepatocellular carcinoma will be enrolled for regorafenib combined with PD-1 inhibitor therapy.In the absence of any of the following conditions, such as withdrawal of informed consent by subjects, intolerable drug side effects, or the investigator's determination that further study is not appropriate, the expected study treatment for each subject will continue until radiologically confirmed tumor progression. Efficacy indicators and safety indicators will be observed during the trial.
- Conditions
- Hepatocellular Carcinoma, Regorafenib, PD-1 Inhibitor
- Being tested
- Regorafenib, PD-1 inhibitor
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called BAY 73-4506, Stivarga
Regorafenib, 120 mg, once a day, 3 weeks on/1 week off
PD-1 inhibitorDrug
Also called Camrelizumab (AiRuiKa™)、Toripalimab、Pembrolizumab(Keytruda)
Camrelizumab: 200mg (BW ≥ 50 kg) or 3 mg/kg (BW < 50 kg) Toripalimab: 240mg is given through intravenous drip every 3 weeks on Day 1 of each course of treatment.
Pembrolizumab: 200mg is given through intravenous drip every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib plus PD-1 inhibitor | Experimental | Regorafenib (BAY 73-4506, Stivarga®) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF).
Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma.
Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers.
Pembrolizumab (Keytruda) the programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. Receives: Drug: Regorafenib; Drug: PD-1 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause
Measured: one year
Secondary outcomes (8)
Objective Response Rate (ORR)
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
Measured: one year
Complete response (CR)
Disappearance of all target lesions, no appearance of new lesions, and normalization of tumor markers last for at least 4 weeks.
Measured: one year
Partial response (PR)
Sum of the maximum diameters of target lesions is reduced by at least 30%, which lasts for at least 4 weeks.
Measured: one year
Overall survival (OS)
It is the time from when a subject is clearly enrolled to death from any cause.
Measured: one year
Duration of response (DOR)
It is the time from the first-time PR or CR (subject to the earlier one) objectively reported to the first-time disease progression or death.
Measured: one year
Percentage of patients with stable disease (SD) ≥ 4 weeks
It is specifically referred to the percentage of patients with identified SD that can be evaluated for efficacy.
Measured: one year
Progression-free survival rate at 3 months
It's the percentage of patients with no disease progression or died from any cause after 3 months of treatment with combination of regorafenib and PD-1 inhibitor in the total number of patients whose efficacy can be evaluated.
Measured: 6 months
Mortality at 12 months
It's the percentage of patients who died of any cause after 12 months treatment with combination of regorafenib and PD-1 inhibitor in total enrolled patients.
Measured: one year and a half
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2021
- Study start1 Oct 2021
- Primary completion1 Nov 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05048017
- Sponsor's protocol ID
- JS-3039
- Status last verified
- Jan 2023
- First submitted
- 17 Aug 2021
- Last updated
- 29 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, Allen C, Alsharif U, Alvis-Guzman N, Amini E, Anderson BO, Aremu O, Artaman A, Asgedom SW, Assadi R, Atey TM, Avila-Burgos L, Awasthi A, Ba Saleem HO, Barac A, Bennett JR, Bensenor IM, Bhakta N, Brenner H, Cahuana-Hurtado L, Castaneda-Orjuela CA, Catala-Lopez F, Choi JJ, Christopher DJ, Chung SC, Curado MP, Dandona L, Dandona R, das Neves J, Dey S, Dharmaratne SD, Doku DT, Driscoll TR, Dubey M, Ebrahimi H, Edessa D, El-Khatib Z, Endries AY, Fischer F, Force LM, Foreman KJ, Gebrehiwot SW, Gopalani SV, Grosso G, Gupta R, Gyawali B, Hamadeh RR, Hamidi S, Harvey J, Hassen HY, Hay RJ, Hay SI, Heibati B, Hiluf MK, Horita N, Hosgood HD, Ilesanmi OS, Innos K, Islami F, Jakovljevic MB, Johnson SC, Jonas JB, Kasaeian A, Kassa TD, Khader YS, Khan EA, Khan G, Khang YH, Khosravi MH, Khubchandani J, Kopec JA, Kumar GA, Kutz M, Lad DP, Lafranconi A, Lan Q, Legesse Y, Leigh J, Linn S, Lunevicius R, Majeed A, Malekzadeh R, Malta DC, Mantovani LG, McMahon BJ, Meier T, Melaku YA, Melku M, Memiah P, Mendoza W, Meretoja TJ, Mezgebe HB, Miller TR, Mohammed S, Mokdad AH, Moosazadeh M, Moraga P, Mousavi SM, Nangia V, Nguyen CT, Nong VM, Ogbo FA, Olagunju AT, Pa M, Park EK, Patel T, Pereira DM, Pishgar F, Postma MJ, Pourmalek F, Qorbani M, Rafay A, Rawaf S, Rawaf DL, Roshandel G, Safiri S, Salimzadeh H, Sanabria JR, Santric Milicevic MM, Sartorius B, Satpathy M, Sepanlou SG, Shackelford KA, Shaikh MA, Sharif-Alhoseini M, She J, Shin MJ, Shiue I, Shrime MG, Sinke AH, Sisay M, Sligar A, Sufiyan MB, Sykes BL, Tabares-Seisdedos R, Tessema GA, Topor-Madry R, Tran TT, Tran BX, Ukwaja KN, Vlassov VV, Vollset SE, Weiderpass E, Williams HC, Yimer NB, Yonemoto N, Younis MZ, Murray CJL, Naghavi M. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018 Nov 1;4(11):1553-1568. doi: 10.1001/jamaoncol.2018.2706.
PubMed 29860482Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006 May 10;24(14):2137-50. doi: 10.1200/JCO.2005.05.2308.
PubMed 16682732Richman DM, Tirumani SH, Hornick JL, Fuchs CS, Howard S, Krajewski K, Ramaiya N, Rosenthal M. Beyond gastric adenocarcinoma: Multimodality assessment of common and uncommon gastric neoplasms. Abdom Radiol (NY). 2017 Jan;42(1):124-140. doi: 10.1007/s00261-016-0901-x.
PubMed 27645897Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, Henley SJ, Holtzman D, Lake A, Noone AM, Anderson RN, Ma J, Ly KN, Cronin KA, Penberthy L, Kohler BA. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer. 2016 May 1;122(9):1312-37. doi: 10.1002/cncr.29936. Epub 2016 Mar 9.
PubMed 26959385Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
PubMed 29433850Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.
PubMed 18650514Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.
PubMed 27932229Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020 Apr;21(4):571-580. doi: 10.1016/S1470-2045(20)30011-5. Epub 2020 Feb 26.
PubMed 32112738Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res. 2021 Feb 15;27(4):1003-1011. doi: 10.1158/1078-0432.CCR-20-2571. Epub 2020 Oct 21.
PubMed 33087333Yamamoto Y, Matsui J, Matsushima T, Obaishi H, Miyazaki K, Nakamura K, Tohyama O, Semba T, Yamaguchi A, Hoshi SS, Mimura F, Haneda T, Fukuda Y, Kamata JI, Takahashi K, Matsukura M, Wakabayashi T, Asada M, Nomoto KI, Watanabe T, Dezso Z, Yoshimatsu K, Funahashi Y, Tsuruoka A. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell. 2014 Sep 6;6:18. doi: 10.1186/2045-824X-6-18. eCollection 2014.
PubMed 25197551Terme M, Tartour E, Taieb J. VEGFA/VEGFR2-targeted therapies prevent the VEGFA-induced proliferation of regulatory T cells in cancer. Oncoimmunology. 2013 Aug 1;2(8):e25156. doi: 10.4161/onci.25156. Epub 2013 Jun 10.
PubMed 24083078Hume DA, MacDonald KP. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood. 2012 Feb 23;119(8):1810-20. doi: 10.1182/blood-2011-09-379214. Epub 2011 Dec 20.
PubMed 22186992Hoff S, Grünewald S, Röse L, Zopf D. 1198PImmunomodulation by regorafenib alone and in combination with anti PD1 antibody on murine models of colorectal cancer. Ann Oncol 2017;28.
Shigeta K, Matsui A, Kikuchi H, Klein S, Mamessier E, Chen IX, Aoki S, Kitahara S, Inoue K, Shigeta A, Hato T, Ramjiawan RR, Staiculescu D, Zopf D, Fiebig L, Hobbs GS, Quaas A, Dima S, Popescu I, Huang P, Munn LL, Cobbold M, Goyal L, Zhu AX, Jain RK, Duda DG. Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma. J Immunother Cancer. 2020 Nov;8(2):e001435. doi: 10.1136/jitc-2020-001435.
PubMed 33234602Sprinzl MF, Galle PR. Current progress in immunotherapy of hepatocellular carcinoma. J Hepatol. 2017 Mar;66(3):482-484. doi: 10.1016/j.jhep.2016.12.009. Epub 2016 Dec 21. No abstract available.
PubMed 28011330
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma: A Single Arm, Nonrandomized, Single Center Clinical Study
- ClinicalTrials.gov ID
- NCT05048017
- Acronym / sponsor ID
- JS-3039
- Conditions
- Hepatocellular Carcinoma, Regorafenib, PD-1 Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 1 Nov 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 17 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, nonrandomized, single center clinical study to investigate the safety and efficacy of regorafenib combined with PD-1 inhibitor therapy for second-line treatment of hepatocellular carcinoma
Detailed description
To observe and evaluate the efficacy, safety and biomarker analysis of regorafenib combined with PD-1 inhibitor for the second-line treatment of hepatocellular carcinoma.In this study, 20 patients with hepatocellular carcinoma will be enrolled for regorafenib combined with PD-1 inhibitor therapy.In the absence of any of the following conditions, such as withdrawal of informed consent by subjects, intolerable drug side effects, or the investigator's determination that further study is not appropriate, the expected study treatment for each subject will continue until radiologically confirmed tumor progression. Efficacy indicators and safety indicators will be observed during the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib plus PD-1 inhibitor | Experimental | Drug: Regorafenib, Drug: PD-1 inhibitorRegorafenib (BAY 73-4506, Stivarga®) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF). Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. Pembrolizumab (Keytruda) the programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Subjects volunteer to participate in the study, agree to sign their written informed consent, show good compliance and are cooperative with the follow-up.
- There is no gender requirement but age requirement (age>18) for the subjects who sign the informed consent.
- The subjects were diagnosed as advanced hepatocellular carcinoma (HCC) by imaging or histological examination.
- The disease is not suitable for radical surgery and/or local treatment, or disease progression occurs after surgery and/or local treatment.
- The patients with at least one measurable lesion according to RECIST, version1.1, and no local radiotherapy was performed. Results of spiral CT scan (RECIST, version 1.1): LD (lesion) ≥ 10 mm or SD (enlarged lymph node) ≥ 15 mm.
Key exclusion criteria (39 listed)
- The clinical stage is stage IV, and/or patients with hepatobiliary solid tumors with any of the following conditions:
- 1.1 The patient is suitable for surgical radical treatment, 1.2 or, the patient has accepted radical treatment and has no assessable lesion, 1.3 or, the patient has a history of liver transplantation or plans to undergo liver transplantation.
- Patient who is known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components; Patient who is known to be allergic to regorafenib and its components.
- ECOG score ≥ 2 points.
- Patient who has ascites with clinical symptoms, that requires therapeutic abdominal puncture or drainage, or Child-Pugh score > 2 points.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RegorafenibAlso: BAY 73-4506, StivargaRegorafenib, 120 mg, once a day, 3 weeks on/1 week off | Drug | Regorafenib plus PD-1 inhibitor |
| PD-1 inhibitorAlso: Camrelizumab (AiRuiKa™)、Toripalimab、Pembrolizumab(Keytruda)Camrelizumab: 200mg (BW ≥ 50 kg) or 3 mg/kg (BW < 50 kg) Toripalimab: 240mg is given through intravenous drip every 3 weeks on Day 1 of each course of treatment. Pembrolizumab: 200mg is given through intravenous drip every 3 weeks. | Drug | Regorafenib plus PD-1 inhibitor |
Primary outcome
Progression Free Survival (PFS)
Time frame: one year
A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause
8 secondary outcomes
Objective Response Rate (ORR)
Time frame: one year
Complete response (CR)
Time frame: one year
Partial response (PR)
Time frame: one year
Overall survival (OS)
Time frame: one year
Duration of response (DOR)
Time frame: one year
Percentage of patients with stable disease (SD) ≥ 4 weeks
Time frame: one year
Progression-free survival rate at 3 months
Time frame: 6 months
Mortality at 12 months
Time frame: one year and a half
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib and PD-1 inhibitor in people with Hepatocellular Carcinoma and Regorafenib, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hai-Tao Zhao, PhD (+861069156042, zhaoht@pumch.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05048017, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.