MelanomaPhase 1/2NCT05539118
Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma
A Phase 1/2 study testing Recombinant human interferon α1b, Toripalimab and Anlotinib hydrochloride in people with Melanoma, run by Xijing Hospital at 1 site in China.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Recombinant human interferon α1b, Toripalimab and Anlotinib hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2022to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Aged 18-75.
- ECOG performance status of 0 or 1
- Life expectancy ≥ 3 months;
- Histologically or cytologically confirmed diagnosis of unresectable stage IIIc, IIId and IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded)
- Baseline tumor specimens available for NGS analysis or equivalent test results acceptable by the principal investigator.
- Measurable disease by RECIST v1.1 criteria
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- Adequate organ and marrow function (within 4 weeks prior to study treatment initiation):
- A negative urine or plasma β-HCG test result is required at screening for female patients of childbearing potential.
- Contraception is required for patients and their partners throughout the trial and within 1 year after the last dose of study treatment.
- Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
- Be willing to signed a written informed consent document before enrollment.
Who cannot join
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to recombinant human interferon-α1bcombined, toripalimab and anlotinib hydrochloride.
- Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry.
- Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry.
- Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy (such as sunitinib, sorafenib, regorafenib, bevacizumab, imatinib, apatinib) or interferon, herbal supplements.
- Plan to take other systemic or local anti-tumor therapy during the current study
- Systemic treatment with either corticosteroid (> 10 mg /kg prednisone equivalents) or other immunosuppressive medications prior to 2 weeks prior to study dose initiation
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- Known hematologic malignancy, primary brain tumor, sarcoma or any other primary solid tumor unless the disease-free period is over 5 years.
- Imaging confirmed of central nervous system (CNS) metastases with or without meningeal carcinomatosis
- Known severe hypersensitivity reaction of another mono-antibody therapy.
- Known active autoimmune disease requiring systemic treatment (such as corticosteroids or immunosuppressive medications) or related replacement therapies (such as thyroid hormone for hypothyroidism, insulin for diabetes or physiological glucocorticoid replacement therapy for adrenal or pituitary insufficiency) in the past 2 years.
- Individuals with bleeding tendency or under thrombolytic or anticoagulant therapy. Coagulation abnormalities as the following circumstances: INR >1.5；PT > 1.2 ULN；PTT > 1.2 ULN.
- Use of anticoagulants or vitamin K antagonists such as warfarin, heparin or similar drugs
- Obvious hemoptysis or daily hemoptysis above 2.5ml in the past 2 months
- Any condition has potential risk of gastrointestinal bleeding or perforation, such as active gastrointestinal ulcer, known intra luminal metastases,inflammatory bowel disease; known abdominal fistula, gastrointestinal perforation or intraperitoneal abscess 4 weeks prior to entry of the study entry
- Open wounds, ulcers or fractures
- Surgery history within past 4 weeks, except for melanoma removal or partial removal
- Hereditary or acquired bleeding and thrombotic tendency such as hemophilia, thrombocytopenia, hypersplenism
- Uncontrolled hypertension defined as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg despite antihypertension medicine therapy
- Known cardiovascular diseases as follows in the past 6 months (cerebral vascular accident, transient ischemic attack, cardiac arrhythmia（including QTc ≥ 450 ms for males and QTc ≥ 470 ms for females; angina,coronary angioplasty or coronary stent implantation, pulmonary embolism,untreated deep vein thrombosis or anticoagulation treatment less than six weeks,arterial thrombosis; heart failure patients in NYHA class III and IV; above Ⅱ degrees heart block; myocardial infarction unstable arrhythmia, or unstable angina in the past 6 months; cerebral infarction within 3 months; left ventricular ejection fraction (LVEF) is less than 50% and clinically significant pericardial disease indicated by color doppler echocardiography; ECG indicates acute ischemia or active conduction system abnormalities
- Use of medications which might lead to Prolonged QT interval and torsades de pointes
- Other diseases that may affect compliance or interfere with results interpretation including active opportunistic infections or progressing or severe infections , uncontrolled diabetes or pulmonary diseases including interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm. Known HIV or AIDS-related illness, or active HBV, HCV and tuberculosis
- A history of getting a live vaccine within 4 weeks prior to the first dose; a history of hematopoietic stimulating factor therapy such as colony-stimulating factor (CSF) and erythropoietin (EPO) within 2 weeks prior to the first dose; a history of major surgeon except for diagnosis within 4 weeks prior to the first dose
- Diagnosis of a psychiatric or substance abuse disorder
- Individuals who are pregnant or breast-feeding or plan to conceive during the study period
- Any other illness, laboratory abnormality, or situations that in the opinion of the principal investigator would compromise the patients' ability to tolerate treatment or would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Air Force Military Medical University/ Fourth Military Medical University
Xi'an, Shaanxi, 710032
About this study
Official title: Interferon-α1b (IFN-α1b) Combined With Toripalimab and Anlotinib Hydrochloride in Patients With Advanced Unresectable Melanoma
The purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Phase Ib will determine the recommended phase Ⅱ dose for anlotinib hydrochloride. Phase II will evaluate the efficacy and safety of the triple combination regimens.
Read the detailed description
This is a single-arm, single-center Phase Ib/II trial to evaluate the efficacy and safety of the combination of recombinant human interferon α1b plus toripalimab and anlotinib hydrochloride in patients with unresectable Stage IIIc, Stage IIId, and Stage IV melanoma(AJCC 8th). Phase I is to evaluate the dose-limiting toxicities (DLT) and determine the recommended Phase II dose (RP2D) of anlotinib hydrochloride in patients with unresectable advanced melanoma receiving recombinant human interferon α1b 600ug QOD plus toripalimab 240mg Q3W. Anlotinib hydrochloride will be given in a dose descending manner(12mg- 10mg- 8mg). In the phase II study, 30 Phase II will enroll 30 patients. The primary endpoint in the II phase is objective response rate (ORR) and progression-free survival (PFS). The second endpoint is disease control rate (DCR), clinical benefit rate (CBR), duration of response (DOR), and overall survival(OS). The safety profile of this combined IFN-α1b/ toripalimab/anlotinib hydrochloride regimen will be monitored during both phases. Specifically, phase Ib will evaluate dose-limiting toxicities(DLT). Phase II will evaluate the numbers and severity of toxicity per the Criteria for Adverse Events version 5 (CTCAEv) including but not limited to all adverse events (AE).
- Conditions
- Melanoma
- Being tested
- Recombinant human interferon α1b, Toripalimab, Anlotinib hydrochloride
- Keywords
- Melanoma; unresectable; Interferon-alfa1b; Toripalimab; Anlotinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human interferon α1bDrug
Recombinant human interferon α1b is a protein with potent antiviral, antiproliferative and immunomodulatory properties.
ToripalimabDrug
Toripalimab is a recombinant, humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.
Anlotinib hydrochlorideDrug
Anlotinib hydrochloride is a novel oral tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR) and c-kit.
| Study group | Role | What they receive |
|---|---|---|
| Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride | Experimental | Recombinant human interferon α1b administered 600μg every other day. Toripalimab administered 240mg intravenously every three weeks. Anlotinib hydrochloride given 12mg or 10mg or 8mg orally (Daily for two weeks continuously, followed by one week of rest). A recommended phase II dose (RP2D) of anlotinib hydrochloride will be determined. Receives: Drug: Recombinant human interferon α1b; Drug: Toripalimab; Drug: Anlotinib hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Recommended phase II dose (RP2D) of anlotinib hydrochloride
RP2D of anlotinib hydrochloride will be depended according to the dose-limiting toxicities of anlotinib hydrochloride
Measured: 12 weeks after first drug administration
Phase II: Objective response rate (ORR)
proportion of patients with a complete response or partial response to treatment
Measured: Up to 24 months after the last episode
Phase II: progression-free survival (PFS)
time from enrollment to progression or death
Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes (4)
disease control rate (DCR)
the percentage of patients who have achieved complete response, partial response and stable disease to the therapeutic intervention
Measured: Up to 60 months after the last episode
duration of response (DOR)
time from response to progression/death (the earlier event)
Measured: Up to 60 months after the last episode
overall survival(OS)
The median and 3 year OS rate of patients with unresectable advanced melanoma treated with the combination regimen of interferon-α1b, toripalimab, and anlotinib hydrochloride
Measured: From date of enrollment until the date of death from any cause, assessed up to 60 months
Clinical Benefit Rate(CBR)
the proportion of patients with a complete or partial response or with stable disease at Week 24
Measured: Week 0-24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2022
- Study start30 Sep 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Xijing 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guannan Zhu, M.D.;Ph.D, Principal investigator, Xijing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05539118
- Sponsor's protocol ID
- KY20222092-C-1
- Status last verified
- Aug 2022
- First submitted
- 17 Aug 2022
- Last updated
- 14 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interferon-α1b (IFN-α1b) Combined With Toripalimab and Anlotinib Hydrochloride in Patients With Advanced Unresectable Melanoma
- ClinicalTrials.gov ID
- NCT05539118
- Acronym / sponsor ID
- KY20222092-C-1
- Conditions
- Melanoma
- Keywords
- Melanoma; unresectable; Interferon-alfa1b; Toripalimab; Anlotinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- 30 Sep 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 14 Sep 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 purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Phase Ib will determine the recommended phase Ⅱ dose for anlotinib hydrochloride. Phase II will evaluate the efficacy and safety of the triple combination regimens.
Detailed description
This is a single-arm, single-center Phase Ib/II trial to evaluate the efficacy and safety of the combination of recombinant human interferon α1b plus toripalimab and anlotinib hydrochloride in patients with unresectable Stage IIIc, Stage IIId, and Stage IV melanoma(AJCC 8th). Phase I is to evaluate the dose-limiting toxicities (DLT) and determine the recommended Phase II dose (RP2D) of anlotinib hydrochloride in patients with unresectable advanced melanoma receiving recombinant human interferon α1b 600ug QOD plus toripalimab 240mg Q3W. Anlotinib hydrochloride will be given in a dose descending manner(12mg- 10mg- 8mg). In the phase II study, 30 Phase II will enroll 30 patients. The primary endpoint in the II phase is objective response rate (ORR) and progression-free survival (PFS). The second endpoint is disease control rate (DCR), clinical benefit rate (CBR), duration of response (DOR), and overall survival(OS). The safety profile of this combined IFN-α1b/ toripalimab/anlotinib hydrochloride regimen will be monitored during both phases. Specifically, phase Ib will evaluate dose-limiting toxicities(DLT). Phase II will evaluate the numbers and severity of toxicity per the Criteria for Adverse Events version 5 (CTCAEv) including but not limited to all adverse events (AE).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride | Experimental | Drug: Recombinant human interferon α1b, Drug: Toripalimab, Drug: Anlotinib hydrochlorideRecombinant human interferon α1b administered 600μg every other day. Toripalimab administered 240mg intravenously every three weeks. Anlotinib hydrochloride given 12mg or 10mg or 8mg orally (Daily for two weeks continuously, followed by one week of rest). A recommended phase II dose (RP2D) of anlotinib hydrochloride will be determined. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Aged 18-75.
- ECOG performance status of 0 or 1
- Life expectancy ≥ 3 months;
- Histologically or cytologically confirmed diagnosis of unresectable stage IIIc, IIId and IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded)
- Baseline tumor specimens available for NGS analysis or equivalent test results acceptable by the principal investigator.
Key exclusion criteria (25 listed)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to recombinant human interferon-α1bcombined, toripalimab and anlotinib hydrochloride.
- Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry.
- Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry.
- Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy (such as sunitinib, sorafenib, regorafenib, bevacizumab, imatinib, apatinib) or interferon, herbal supplements.
- Plan to take other systemic or local anti-tumor therapy during the current study
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 human interferon α1bRecombinant human interferon α1b is a protein with potent antiviral, antiproliferative and immunomodulatory properties. | Drug | Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride |
| ToripalimabToripalimab is a recombinant, humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth. | Drug | Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride |
| Anlotinib hydrochlorideAnlotinib hydrochloride is a novel oral tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR) and c-kit. | Drug | Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride |
Primary outcome
Phase I: Recommended phase II dose (RP2D) of anlotinib hydrochloride
Time frame: 12 weeks after first drug administration
RP2D of anlotinib hydrochloride will be depended according to the dose-limiting toxicities of anlotinib hydrochloride
Phase II: Objective response rate (ORR)
Time frame: Up to 24 months after the last episode
proportion of patients with a complete response or partial response to treatment
Phase II: progression-free survival (PFS)
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
time from enrollment to progression or death
4 secondary outcomes
disease control rate (DCR)
Time frame: Up to 60 months after the last episode
duration of response (DOR)
Time frame: Up to 60 months after the last episode
overall survival(OS)
Time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
Clinical Benefit Rate(CBR)
Time frame: Week 0-24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
- Individual participant dataSharing planned: Undecided
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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.
Guannan Zhu, M.D.;Ph.D principal investigator
Xijing Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Recombinant human interferon α1b, Toripalimab and Anlotinib hydrochloride in people with Melanoma, run by Xijing 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 11 inclusion and 25 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: opening soon, as of the sponsor's last update on 14 Sep 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 combined 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.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guannan Zhu, M.D.;Ph.D (0086-84775406-8403, to_rain77@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Recommended phase II dose (RP2D) of anlotinib hydrochloride (time frame: 12 weeks after first drug administration). The study lists 3 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 14 Sep 2022.