Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms NeoplasmsPhase 3NCT05647954
A Study of HX008 Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver
A Phase 3 study testing HX008 + TACE, Temozolomide + TACE and Pembrolizumab in people with Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, run by Taizhou Hanzhong biomedical co. LTD at 1 site in China.
Trial summary
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS) and Overall Survival(OS), achieved by HX008 Plus Transcatheter Arterial Chemoembolization (TACE) or Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms
- What is being tested?
- HX008 + TACE, Temozolomide + TACE and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2022to 30 Jun 2025
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily sign the Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
- Males or females, aged 18 to 75 are eligible on the day of signing the informed consent form;
- Subjects with stage IV (M1c) melanoma confirmed by histology with liver metastasis approved by Pathology;
- No prior systemic treatment for Stage IV (M1c) Melanoma with liver Metastatic; except:
- Melanoma with BRAF V600 mutation-positive may receive targeted therapy(e.g., BRAF/MEK inhibitor, alone or in combination) as first-line treatment for advanced or metastatic disease;
- Prior targeted therapy or immunotherapy (e.g., anti-PD-1 monoclonal antibody, anti-CTLA-4 monoclonal antibody or interferon, BRAF/MEK inhibitors, alone or in combination) as adjuvant or neoadjuvant therapy, if no recurrence or metastasis occurred during treatment or within 6 months of treatment termination. Prior adjuvant temozolomide and cisplatin chemotherapy of primary mucosa melanoma, without recurrence or metastasis during treatment or within 6 months of treatment termination.
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- Subjects must have a BRAF-V600 mutation or agree to carry out BRAF-V600 mutation detection during the screening phase ;
- At least one measurable lesion of the subject's liver according to RECIST version 1.1 (Lesions with the longest diameter ≥ 10mm)
- Target lesion has not received prior local treatment, including transarterial embolization (TAE), TACE, transarterial radioembolization (TARE), surgery, radiofrequency ablation (RFA), microwave ablation (MWA), other thermal ablation, percutaneous ethanol injection (PEI), radiation therapy, etc. Subjects who have received prior local treatment for non-target lesions are eligible for the study. Local treatment must be completed at least 4 weeks before randomization.
- Liver function classified as Child-Pugh class A or B with a score ≤ 7, and no history of hepatic encephalopathy；
- Suitability for the TACE procedures and chemotherapeutic agents pre-specified by the research center, without any contraindications;
- Eastern Cooperative Oncology Group (ECOG) of 0 or 1;
- Estimated life expectancy of ≥12 weeks;
- Has sufficient organ and bone marrow function((no blood transfusions allowed for 14 days prior to blood routine, no any cell growth factors or/and platelet-raising drugs) to meet the following laboratory examination standards:
- Absolute neutrophil count (NUT#)≥1.5×10^9/L
- White blood cell count (WBC)≥3×10^9/L
- Platelet count (PLT)≥100×10^9/ L
- Hemoglobin (HGB)≥90 g/L
- Serum creatinine (Scr) ≤1.5×ULN g. ALT、AST ≤5×ULN h. TBIL≤1.5×ULN i.International normalized ratio (INR) ≤ 1.5×ULN; or activated partial thromboplastin time (APTT)≤ 1.5×ULN;(except for patients on anticoagulant therapy);
- Women of childbearing age must have a negative pregnancy test within 72 hours before the first dose of trial treatment. Reproductive men and women of childbearing age are willing to take adequate contraceptive measures (e.g., oral contraceptives, intrauterine contraceptives, sexual abstinence or barrier contraceptives combined with spermicide) from signing the informed consent form to 12 months after the last administration of the trial drug;
- The informed consent was voluntarily signed and the expected compliance was good.
Who cannot join
- Malignant melanoma of ocular origin;
- Investigator-identified contraindications to TACE (e.g., portal vein obstruction without formation of collateral vessels, etc.);
- Liver lesions ≥ 10 cm in any dimension, more than 10 lesions on imaging evaluation, or liver lesions representing ≥ 50% of the liver volume.
- Subjects diagnosed with any other malignancy within 3 years before randomization, except for malignancies with a low risk of metastasis and death (5-year survival rate > 90%), such as adequately basal cell or squamous cell skin cancer or carcinoma in situ of the cervix and other carcinomas in situ;
- Had active autoimmune disease (except for psoriasis), that has required systemic treatment in the past 2 years((e.g., corticosteroids or immunosuppressive drugs). Except for alternative therapies (eg, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency);
- Need to receive systemic corticosteroids (dose equivalent to > 10 mg prednisone/day) or other immunosuppressive drugs within 14 days before enrollment or during the study period. Those under the following conditions are eligible:
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- Locally external use or inhaled corticosteroids;
- short-term (≤7 days) use of glucocorticoids for the prevention or treatment of nonautoimmune allergic diseases;
- Had received anti-tumor treatment within 4 weeks before randomization, or have not recovered from the toxicity of the last treatment (except for hair loss of Grade 2 and neurotoxicity of Grade 1);
- Had received radiotherapy within 2 weeks before randomization， or had prior radiation therapy, or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to previous radiation therapy;
- Had received major surgery, open biopsy, or severe trauma within 4 weeks before randomization; Definition of major surgery: the minimum of 3 weeks of post-operative recovery time is required to undergo this study;
- Had severe infection within 4 weeks or active infection requiring IV infusion or oral administration of antibiotics within 2 weeks before randomization;
- Had participated in other drug or device clinical trials within 4 weeks before randomization;
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or found during the screening phase. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks, have no evidence of new or enlarging brain metastases, and also are off steroids 14 days before dosing with study medication may participate. Subjects with known untreated, asymptomatic brain metastases (ie, Lesions with numbers ≤ 3, and Lesions with the longest diameter ≤ 1 cm, ) may participate;
- Has pleural effusion, pericardial effusion, or uncontrolled ascites requiring repeated drainage (once a month or more);
- Has incomplete intestinal obstruction, active gastrointestinal bleeding, or perforation;
- Has a history or current interstitial pneumonia, or current non--infectious pneumonitis treatment with corticosteroids;
- Has uncontrolled cardiovascular disease, including but not limited to:
- heart failure greater than New York Heart Association (NYHA) class II
- unstable angina pectoris
- has myocardial infarction within 1 year
- supraventricular or ventricular arrhythmias with clinical significance poorly controlled without or despite clinical intervention;
- Has uncontrolled systemic diseases, for instance, diabetes(Fasting Plasma Glucose ≥ 8.9 mmol/L or hypertension(systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg);
- Subjects with active tuberculosis;
- History of human immunodeficiency virus infection, acquired or congenital immunodeficiency disease, organ transplantation, or stem cell transplantation;
- Subjects with chronic hepatitis B or active hepatitis C. Except for Hepatitis B virus carriers or those with stable hepatitis B after drug treatment with DNA titer no higher than 500 IU/ml or copy number <2500 copies/ml, and cured hepatitis C patients (HCV RNA test negative);
- Known to be allergic to macromolecular protein agents or monoclonal antibodies. Known to have a history of severe allergies to any of the chemotherapy drugs in the study ;
- Alcohol dependence or drug abuse within the past 1 year;
- Has received a live vaccine within 30 days before the first dose of trial treatment. Subjects are permitted to receive inactivated vaccines including those for seasonal influenza, intranasal influenza vaccines are not allowed;
- Other reasons disqualifying the entering of this study are based on the investigators' evaluation.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Cancer hospital
Beijing, Beijing Municipality, 100142
Jun Guo, MD, +861088196348, guoj307@126.com
About this study
Official title: A Randomized, Open-Label, Multicenter, Phase III Study of HX008 (a Humanized Monoclonal Antibody Against PD-1) Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS) and Overall Survival(OS), achieved by HX008 Plus Transcatheter Arterial Chemoembolization (TACE) or Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver.
- Being tested
- HX008 + TACE, Temozolomide + TACE, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HX008 + TACEDrug
HX008 Subjects receive HX008 200 mg intravenous (IV) ,day1,every 3 weeks (Q3W) Procedure: TACE cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions).
Temozolomide + TACEDrug
Temozolomide Subjects receive Temozolomide 200 mg/sqm intravenous (IV),day1-5, every 3 weeks (Q3W)
Procedure: TACE :
cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions).
PembrolizumabDrug
Subjects receive Pembrolizumab 2 mg/kg intravenous (IV),day1, every 3 weeks (Q3W)
| Study group | Role | What they receive |
|---|---|---|
| HX008 Plus Transcatheter Arterial Chemoembolization(TACE) | Experimental | Not described Receives: Drug: HX008 + TACE |
| Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) | Active comparator | Not described Receives: Drug: Temozolomide + TACE |
| Pembrolizumab | Active comparator | Not described Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) by Independent Review Committee(IRC)
PFS, defined as the time from randomization to the first documented disease.(HX008 + TACE vs Temozolomide + TACE)
Measured: 2 years
Overall Survival (OS)
OS, defined as the duration from the start of treatment to death of any cause.(HX008 + TACE vs Temozolomide + TACE)
Measured: 2 years
Secondary outcomes (7)
Progression-free Survival (PFS) by Investigators
PFS, defined as the time from randomization to the first documented disease.(HX008 + TACE vs Temozolomide + TACE)
Measured: 2 years
Objective Response Rate (ORR)
ORR, defined as the percentage of subjects achieving complete response (CR) and partial response (PR).
Measured: 2 years
Disease Control Rate (DCR)
DCR, defined as the proportion of subjects achieving CR, PR, and Stable disease（SD) after treatment.
Measured: 2 years
Duration of Response (DOR)
DOR, defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.
Measured: 2 years
Progression-free Survival (PFS) by IRC or investigators
PFS, defined as the time from randomization to the first documented disease.(HX008 + TACE vs Pembrolizumab)
Measured: 2 years
Overall Survival (OS)
OS, defined as the duration from the start of treatment to death of any cause.(HX008 + TACE vs Pembrolizumab)
Measured: 2 years
Adverse events
Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0,etc.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2022
- Study start31 Dec 2022 (estimated)
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms NeoplasmsStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taizhou Hanzhong biomedical co. LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jun Guo, MD, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05647954
- Sponsor's protocol ID
- HX008-Ⅲ-MM-01
- Status last verified
- Nov 2022
- First submitted
- 28 Nov 2022
- Last updated
- 13 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Multicenter, Phase III Study of HX008 (a Humanized Monoclonal Antibody Against PD-1) Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver
- ClinicalTrials.gov ID
- NCT05647954
- Acronym / sponsor ID
- HX008-Ⅲ-MM-01
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Taizhou Hanzhong biomedical co. LTDIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2022 (estimated)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 13 Dec 2022 (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.
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS) and Overall Survival(OS), achieved by HX008 Plus Transcatheter Arterial Chemoembolization (TACE) or Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HX008 Plus Transcatheter Arterial Chemoembolization(TACE) | Experimental | Drug: HX008 + TACE |
| Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) | Active comparator | Drug: Temozolomide + TACE |
| Pembrolizumab | Active comparator | Drug: Pembrolizumab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Voluntarily sign the Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
- Males or females, aged 18 to 75 are eligible on the day of signing the informed consent form;
- Subjects with stage IV (M1c) melanoma confirmed by histology with liver metastasis approved by Pathology;
- No prior systemic treatment for Stage IV (M1c) Melanoma with liver Metastatic; except:
- Subjects must have a BRAF-V600 mutation or agree to carry out BRAF-V600 mutation detection during the screening phase ;
Key exclusion criteria (30 listed)
- Malignant melanoma of ocular origin;
- Investigator-identified contraindications to TACE (e.g., portal vein obstruction without formation of collateral vessels, etc.);
- Liver lesions ≥ 10 cm in any dimension, more than 10 lesions on imaging evaluation, or liver lesions representing ≥ 50% of the liver volume.
- Subjects diagnosed with any other malignancy within 3 years before randomization, except for malignancies with a low risk of metastasis and death (5-year survival rate > 90%), such as adequately basal cell or squamous cell skin cancer or carcinoma in situ of the cervix and other carcinomas in situ;
- Had active autoimmune disease (except for psoriasis), that has required systemic treatment in the past 2 years((e.g., corticosteroids or immunosuppressive drugs). Except for alternative therapies (eg, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency);
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 |
|---|---|---|
| HX008 + TACEHX008 Subjects receive HX008 200 mg intravenous (IV) ,day1,every 3 weeks (Q3W) Procedure: TACE cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions). | Drug | HX008 Plus Transcatheter Arterial Chemoembolization(TACE) |
| Temozolomide + TACETemozolomide Subjects receive Temozolomide 200 mg/sqm intravenous (IV),day1-5, every 3 weeks (Q3W) Procedure: TACE : cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions). | Drug | Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) |
| PembrolizumabSubjects receive Pembrolizumab 2 mg/kg intravenous (IV),day1, every 3 weeks (Q3W) | Drug | Pembrolizumab |
Primary outcome
Progression-free Survival (PFS) by Independent Review Committee(IRC)
Time frame: 2 years
PFS, defined as the time from randomization to the first documented disease.(HX008 + TACE vs Temozolomide + TACE)
Overall Survival (OS)
Time frame: 2 years
OS, defined as the duration from the start of treatment to death of any cause.(HX008 + TACE vs Temozolomide + TACE)
7 secondary outcomes
Progression-free Survival (PFS) by Investigators
Time frame: 2 years
Objective Response Rate (ORR)
Time frame: 2 years
Disease Control Rate (DCR)
Time frame: 2 years
Duration of Response (DOR)
Time frame: 2 years
Progression-free Survival (PFS) by IRC or investigators
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Adverse events
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Individual participant dataSharing planned: No
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.
Jun Guo, MD principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HX008 + TACE, Temozolomide + TACE and Pembrolizumab in people with Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, run by Taizhou Hanzhong biomedical co. LTD 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 21 inclusion and 30 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 13 Dec 2022. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Jun Guo, MD (861088196348, guoj307@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) by Independent Review Committee(IRC) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Dec 2022.