Melanoma Stage IVPhase 1NCT05070221
Study of Oncolytic Virus in Combination With HX-008 and Axitinib in Melanoma Patients With Liver Metastasis
A Phase 1 study testing Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Recombinant humanized anti-PD-1 monoclonal antibody for injection and Axitinib in people with Melanoma Stage IV, run by Peking University Cancer Hospital & Institute.
Trial summary
Malignant melanoma, is a kind of malignant tumor derived from melanocytes. It is common in skin, mucous membrane, eye choroid and other parts. Melanoma is one of the fastest growing malignant tumors with an annual incidence rate of 3-5%. In 2012, there were 232000 new cases of melanoma and 55000 deaths worldwide. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma Stage IV
- What is being tested?
- Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Recombinant humanized anti-PD-1 monoclonal antibody for injection and Axitinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2021to 31 Dec 2023
- Phase
- Phase 1
- 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 Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
- Male and female, 18-75 years old (including boundary value);
- Histologically confirmed stage IV melanoma with liver metastasis who lacks or becomes refractory to standard treatment;
- Eastern Cooperative Oncology Group (ECOG) Performance Status is 0 or 1;
- Expected survival at least 3 months;
- The interval between the first administration and previous treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy and biotherapy for melanoma) in the past is over 4 weeks, and has recovered to grade 1 from the adverse reactions of previous treatment;
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- At least one measurable or evaluable lesion;
- Liver metastasis has lesions suitable for intratumoral injection;
- Asymptomatic central nervous system metastasis or asymptomatic brain metastasis after treatment must be confirmed by CT / MRI that there is no disease progression, stable for at least 3 months, and no steroid treatment for at least 4 weeks;
- Appropriate organs and hematopoietic function according to the following laboratory tests: neutrophil absolute count (neut#) ≥ 2.0 × 109/L； Absolute white blood cell count (WBC) ≥ 3.0 × 109/L； Platelet ≥ 100 × 109/L； Hemoglobin ≥ 90g / L; Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 5 times ULN; Serum total bilirubin (TBIL) ≤ 1.5 times ULN; International normalized ratio (INR) ≤ 1.5 times ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (except for patients undergoing anticoagulant therapy);
- Male patients and female subjects of childbearing age should agree to take effective contraceptive measures from the signing of informed consent to 3 months after the last administration;
- Patients with herpes need 3 months after the end of herpes treatment.
Who cannot join
- Patients with a history of primary uveal melanoma or any other (including unknown primary) malignancy within 5 years before the first administration of the trial treatment.
- Note: 1 or 2 stage skin basal / squamous cell carcinoma, superficial bladder cancer or orthotopic carcinoma receiving potentially curative treatment are the most effective treatments;
- Liver lesions are not suitable for intratumoral injection or do not meet the injection volume requirements;
- Patients who had received anti herpes simplex virus treatment within 4 weeks before the first administration of the trial treatment, such as acyclovir, ganciclovir, valacyclovir, arabine adenosine, etc;
- Patients with active or history of autoimmune diseases that may recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (such as organ transplantation and immunosuppressive treatment). However, subjects with the following diseases are allowed to be included in the group:
- stable type 1 diabetic patients after a fixed dose of insulin.
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- autoimmune hypothyroidism or Hashimoto's thyroid inflammation requiring only hormone replacement therapy;
- skin diseases that do not require systemic treatment (such as eczema, skin rash accounting for less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.);
- celiac disease that has been controlled;
- any other disease that will not recur without external inducing factors;
- Patients with major surgery are expected to include a 28 day screening period during the study period;
- Patients requiring systemic corticosteroids (equivalent to > 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. However, you are allowed to join the group under the following conditions:
- subjects were allowed to use topical or inhaled glucocorticoids;
- allow short-term (≤ 7 days) use of glucocorticoids to prevent or treat non autoimmune allergic diseases;
- Patients with active gastrointestinal ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding and perforation;
- Patients suffering from interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease, acute radiation pneumonia, etc;
- Uncontrolled stable systemic diseases such as cardiovascular and cerebrovascular diseases, hypertension, diabetes, tuberculosis and so on.
- History of infection with human immunodeficiency virus, or suffer from other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation or stem cell transplantation;
- patients with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA copy number >1x103 copy /mL;
- Patients with hepatitis C virus (HCV) antibody positive or human immunodeficiency virus (HIV) antibody positive;
- Patients with severe infection within 4 weeks before the first administration, or patients with active infection requiring intravenous antibiotic treatment within 2 weeks before the first administration, and patients with unexplained fever > 38.5 ℃ before the first administration;
- Patients known to have severe allergic reactions to herpes virus, macromolecular protein preparation / monoclonal antibody, or any known test drug components (CTCAE v5.0 grade is greater than grade 3);
- Participated in clinical trials of other drugs within 4 weeks before the first administration;
- Alcohol addicts or have a history of drug abuse or drug abuse in recent 1 year;
- Having a clear history of neurological or mental disorders, such as epilepsy, dementia, poor compliance, or peripheral nervous system disorders;
- Pregnant or lactating women;
- Patients who received live attenuated vaccine within 30 days before the first administration;
- The researchers believe that patients who are not suitable to participate in the trial for other reasons.
Trial locations and contacts
No sites are listed yet.
Chuanliang Cui, MD contact
About this study
Official title: Safety and Efficacy Study of Oncolytic Virus（Intratumoral Injection）in Combination With HX-008（Intravenous Injection）and Axitinib in Melanoma Patients With Liver Metastasis Who Lack or Become Refractory to Standard Treatment
Malignant melanoma, is a kind of malignant tumor derived from melanocytes. It is common in skin, mucous membrane, eye choroid and other parts. Melanoma is one of the fastest growing malignant tumors with an annual incidence rate of 3-5%. In 2012, there were 232000 new cases of melanoma and 55000 deaths worldwide. Though, the incidence rate of melanoma is relatively low in China, it has been increasing rapidly in recent years. Melanoma has seriously endangering the health of Chinese people.
Patients with stage Ⅳ melanoma have a poor prognosis. According to statistics, the median survival time of stage M1a melanoma is 15 months, while stage M1b is 8 months. The median survival time of bone metastasis melanoma is 6 months, while liver and brain metastasis is 4 months. The overall median survival time of metastatic melanoma is only 7.5 months, and the 2-year survival rate is 15%.
Read more
For patients with advanced melanoma, dacarbazine is the only chemotherapy drug approved by NMPA, but its overall effective rate is only 13.4%, and the median survival time is 5.6 ~ 11 months.
Therapies(new drugs or new combination treatments)with higher remission rate and longer survival are urgently needed for patients with advanced melanoma.
Read the detailed description
This study is a single-center, non-randomized,open-label study to evaluate safety and efficacy of recombinant human GM-CSF herpes simplex virus（intratumoral injection） in combination with recombinant humanized anti-PD-1 monoclonal antibody (intravenous injection) and Axitinib for liver metastasis in stage IV melanoma.
This study is planned to enroll 30-45 patients with stage IV liver metastasis melanoma who lack or become refractory to standard treatment.
This study set scientific inclusion/exclusion criteria. Patients could be included in the group for treatment only after being strictly reviewed by researcher. The clinical research associate(CRA) will regularly monitor the research data during the whole study.
- Conditions
- Melanoma Stage IV
- Being tested
- Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Recombinant humanized anti-PD-1 monoclonal antibody for injection, Axitinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF)Drug
Also called OH2
less than 8mL/time，Q2W，i.t.；
Recombinant humanized anti-PD-1 monoclonal antibody for injectionDrug
Also called HX-008
200mg/time，Q3W，i.v.；
AxitinibDrug
Also called Inlyta®
5mg，bid，p.o.；
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients histologically confirmed mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day). Receives: Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF); Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection; Drug: Axitinib |
| Arm B | Experimental | Patients histologically confirmed non-mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day). Receives: Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF); Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection; Drug: Axitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR(6 months)
ORR(6 month) is defined as the proportion of subjects with complete response (CR) and partial response (PR) after 6 months of treatment.
Measured: From first dose up to 6 months, approximately.
Secondary outcomes (5)
DCR(6 months)
DCR(6 month) is defined as the proportion of subjects with complete response (CR) , partial response (PR) and stable disease(SD) after 6 months of treatment.
Measured: Time Frame: From first dose up to 6 months, approximately.
PFS
PFS is defined as the time from the beginning of treatment to tumor progression or death from any cause.
Measured: From first dose up to 12 months, approximately.
OS
OS is defined as the time from the beginning of treatment to death due to any cause.
Measured: From first dose up to 12 months, approximately.
overall survival rate（one year）
defined as the proportion of patients who survived after 1 year of treatment
Measured: From first dose up to 12 months, approximately.
overall survival rate（two years）
defined as the proportion of patients who survived after 2 year of treatment
Measured: From first dose up to 24 months, approximately.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2021
- Study start1 Oct 2021 (estimated)
- Primary completion31 Oct 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IVStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Guo, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05070221
- Sponsor's protocol ID
- BH-OH2-014
- Status last verified
- Sep 2021
- First submitted
- 27 Sep 2021
- Last updated
- 7 Oct 2021
- Results posted
- No
- Data monitoring committee
- 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 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Study of Oncolytic Virus（Intratumoral Injection）in Combination With HX-008（Intravenous Injection）and Axitinib in Melanoma Patients With Liver Metastasis Who Lack or Become Refractory to Standard Treatment
- ClinicalTrials.gov ID
- NCT05070221
- Acronym / sponsor ID
- BH-OH2-014
- Conditions
- Melanoma Stage IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 1 Oct 2021 (estimated)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 7 Oct 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.
Malignant melanoma, is a kind of malignant tumor derived from melanocytes. It is common in skin, mucous membrane, eye choroid and other parts. Melanoma is one of the fastest growing malignant tumors with an annual incidence rate of 3-5%. In 2012, there were 232000 new cases of melanoma and 55000 deaths worldwide. Though, the incidence rate of melanoma is relatively low in China, it has been increasing rapidly in recent years. Melanoma has seriously endangering the health of Chinese people.
Patients with stage Ⅳ melanoma have a poor prognosis. According to statistics, the median survival time of stage M1a melanoma is 15 months, while stage M1b is 8 months. The median survival time of bone metastasis melanoma is 6 months, while liver and brain metastasis is 4 months. The overall median survival time of metastatic melanoma is only 7.5 months, and the 2-year survival rate is 15%.
For patients with advanced melanoma, dacarbazine is the only chemotherapy drug approved by NMPA, but its overall effective rate is only 13.4%, and the median survival time is 5.6 ~ 11 months.
Therapies(new drugs or new combination treatments)with higher remission rate and longer survival are urgently needed for patients with advanced melanoma.
Detailed description
This study is a single-center, non-randomized,open-label study to evaluate safety and efficacy of recombinant human GM-CSF herpes simplex virus（intratumoral injection） in combination with recombinant humanized anti-PD-1 monoclonal antibody (intravenous injection) and Axitinib for liver metastasis in stage IV melanoma.
This study is planned to enroll 30-45 patients with stage IV liver metastasis melanoma who lack or become refractory to standard treatment.
This study set scientific inclusion/exclusion criteria. Patients could be included in the group for treatment only after being strictly reviewed by researcher. The clinical research associate(CRA) will regularly monitor the research data during the whole study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection, Drug: AxitinibPatients histologically confirmed mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day). |
| Arm B | Experimental | Drug: Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Drug: Recombinant humanized anti-PD-1 monoclonal antibody for injection, Drug: AxitinibPatients histologically confirmed non-mucosal melanoma will get OH2 （once every two weeks）and HX-008 (once every three weeks)and Axitinib (once every day). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Voluntarily sign Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
- Male and female, 18-75 years old (including boundary value);
- Histologically confirmed stage IV melanoma with liver metastasis who lacks or becomes refractory to standard treatment;
- Eastern Cooperative Oncology Group (ECOG) Performance Status is 0 or 1;
- Expected survival at least 3 months;
Key exclusion criteria (28 listed)
- Patients with a history of primary uveal melanoma or any other (including unknown primary) malignancy within 5 years before the first administration of the trial treatment.
- Note: 1 or 2 stage skin basal / squamous cell carcinoma, superficial bladder cancer or orthotopic carcinoma receiving potentially curative treatment are the most effective treatments;
- Liver lesions are not suitable for intratumoral injection or do not meet the injection volume requirements;
- Patients who had received anti herpes simplex virus treatment within 4 weeks before the first administration of the trial treatment, such as acyclovir, ganciclovir, valacyclovir, arabine adenosine, etc;
- Patients with active or history of autoimmune diseases that may recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (such as organ transplantation and immunosuppressive treatment). However, subjects with the following diseases are allowed to be included in the group:
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 |
|---|---|---|
| Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF)Also: OH2less than 8mL/time，Q2W，i.t.； | Drug | Arm A, Arm B |
| Recombinant humanized anti-PD-1 monoclonal antibody for injectionAlso: HX-008200mg/time，Q3W，i.v.； | Drug | Arm A, Arm B |
| AxitinibAlso: Inlyta®5mg，bid，p.o.； | Drug | Arm A, Arm B |
Primary outcome
ORR(6 months)
Time frame: From first dose up to 6 months, approximately.
ORR(6 month) is defined as the proportion of subjects with complete response (CR) and partial response (PR) after 6 months of treatment.
5 secondary outcomes
DCR(6 months)
Time frame: Time Frame: From first dose up to 6 months, approximately.
PFS
Time frame: From first dose up to 12 months, approximately.
OS
Time frame: From first dose up to 12 months, approximately.
overall survival rate（one year）
Time frame: From first dose up to 12 months, approximately.
overall survival rate（two years）
Time frame: From first dose up to 24 months, approximately.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
- Individual participant dataSharing planned: No
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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.
Chuanliang Cui, MD contact
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant Oncolytic HSV-2 Therapeutic Injecta (Vero Cell) for Human Use (rHSV2hGM-CSF), Recombinant humanized anti-PD-1 monoclonal antibody for injection and Axitinib in people with Melanoma Stage IV, run by Peking University Cancer Hospital & Institute.
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 12 inclusion and 28 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 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 (86-10-88121122, guoj307@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR(6 months) (time frame: From first dose up to 6 months, approximately.). 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 7 Oct 2021.