Solid TumorPhase 1NCT03313219
Pharmacokinetics and Tolerancebility Studies of Gentuximab Injection in the Treatment ofPatients With Late Recurrence of Metastatic Solid Tumors in China
A Phase 1 study testing Gentuximab Injection in people with Solid Tumor, run by Changchun GeneScience Pharmaceutical Co., Ltd. at 1 site in China.
Trial summary
The primary objective is to evaluate the safety and, tolerabilitytolerance, pharmacokinetices and immunogenicity of escalating single doses and subsequent multiple dose of Gentuximab Injection in patients with late recurrence of metastatic solid tumors and to determine the maximum tolerated dose（MTD） and dose limiting… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Gentuximab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 11 Oct 2017to Dec 2019
- 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
- Male or female. aged between 18 and 75 years.
- Participants with histopathologically or cytologically diagnosed advanced or metastatic malignant solid tumor.
- Did not respond to standard therapy or no standard therapy is available.
- At least one Measurable lesion.
- At least 4 weeks after the last chemotherapy (at least 14 days from the last medication with oral fluorouracil drugs), at least 6 weeks after the last medication with mitomycin C and nitrosourea; wait for at least a elution periods for 5 half-life if anti-tumor biological products are dosed.
- The subject should restore to ≤1 level (NCI-CTCAE4.03) if they have toxicity response caused by previous treatment, except hair loss.
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- Performance status (PS) score, ECOG0-1 level.
- A life expectancy of >3 months.
- Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin concentration ≥90g/L (allowing blood transfusion); and platelet count ≥100×109/L.
- Adequate hepatic function, as defined by: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (liver metastases patients ALT ≤ 5 × ULN, AST ≤ 5 × ULN, TBIL ≤ 3 × ULN).
- Adequate renal function, as defined by: serum creatinine level≤ 1.5 × ULN, creatinine clearance ≥ 60ml / min.
- Adequate coagulation function, as defined by: International normalized ratio (INR) ≤1.5× ULN, activated partial thromboplastin time (aPTT) ≤1.5 x ULN.
- Qualified subjects (male and female) who have fertility must agree to use reliable contraceptive methods (hormones or barriers or abstinence) during the trial and at least 12 weeks after the last administration. Female in childbearing age must be negative for blood pregnancy test within 7 days prior to enrollment.
- Subjects should be informed of the study prior to trial and voluntarily signed a written informed consent.
- The subject is able to communicate well with the investigator and be able to complete the study in accordance with the study.
Who cannot join
- Subject who has HIV infection, active hepatitis B, hepatitis C or syphilis infection.
- Subject is histologically confirmed as lung squamous cell carcinoma or squamous cell carcinoma of the head and neck, or subjects with lung metastases and metastases with the void ，or bleeding tendency or risk which researchers conformed.
- Has known alcohol or drug dependency.
- Has participated in a clinical study of a non-approved experimental agent within 4 weeks prior to study entry.
- Have serious infection need antibiotic therapy by intravenous injection .
- Has documented and/or symptomatic brain or leptomeningeal metastases.
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- Has urinary protein prior to study entry (urinary protein ≥1+，need to detection 24h urinary protein，if 24h urinary protein≥1g,then entry not allowed）.
- Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess <6 months before study entry.
- Has a serious or nonhealing wound, ulcer, or bone fracture.
- Has undergone major surgery within 28 days before study entry (not including needle biopsy) or have had significant trauma.
- Has active bleeding within 3 months before enrollment.
- Venous thrombosis currently required treatment; myocardial infarction, stroke, or other severe arterial thromboembolic events occurred within 6 months before enrollment.
- Using anticoagulation and antiplatelet drugs.
- Left ventricular ejection fraction ≤ 50%, New York Heart Association (NYHA) Grade II and above heart failure, uncontroled hypertension (systolic blood pressure> 140 mmHg and/ or diastolic blood pressure> 90 mmHg after treatment with a drug) .
- Is pregnant (confirmed by urine or serum pregnancy test) or lactating.
- Has a known serious allergy reaction to recombination monoclonal antibody (MAb) drug, ,or infusion reaction.
- Is not considered to be suitable for this study, in the opinion of the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics and Tolerabilitynce Studies of Gentuximab (Recombinant Anti-VEGFR2 Human-mouse Chimeric Monoclonal Antibody) Injection in the Treatment of Late Recurrence of Metastatic Solid Tumors in China: An Open-label，Non-randomised，Uncontrolled，Dose-escalation，Single Center，Pphase Ia Study in Patients With Late Recurrence of Metastatic Solid Tumors in China
The primary objective is to evaluate the safety and, tolerabilitytolerance, pharmacokinetices and immunogenicity of escalating single doses and subsequent multiple dose of Gentuximab Injection in patients with late recurrence of metastatic solid tumors and to determine the maximum tolerated dose（MTD） and dose limiting toxicities（DLT）.with single and subsequent multiple intravenous infusion in patients with late recurrence of metastatic solid tumors and to provide a basis for the protocol design of later clinical trials.
The secondary objective is to evaluate the pharmacokinetics, pharmacodynamics and immunogenicity, and tumor response of multiple dose of Gentuximab Injection in patients with late recurrence of metastatic solid tumors.
Read the detailed description
The safety profile of Gentuximab Injection will be explored together with the pharmacokinetics, pharmacodynamics and tumour response to treatment with Gentuximab Injection to recommend the dosing regimen for further clinical studies. The pharmacokinetic properties of Gentuximab Injection will be evaluated after single and multiple dose administrations at different dose levels.
- Conditions
- Solid Tumor
- Being tested
- Gentuximab Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gentuximab InjectionDrug
Gentuximab Injection (Recombinant anti-VEGFR2 human-mouse chimeric monoclonal antibody injection)
| Study group | Role | What they receive |
|---|---|---|
| Gentuximab Injection | Experimental | Patients are assigned to a dose level at the time of study entry and scheduled to receive i.v. of a single dose. The patient enter the subsequent multiple dose i.v. in a 7-day cycle if no DLT in 21 days after the first dose. The study period of each subject will be up to 4 cycles until the tumor progression or unacceptable toxicity. The MTD will be determined by assessing DLT in each cohort from cohort 1 to 6, using a 3+3 dose escalation model. Cohort A begin at 4mg/kg IV and the dose escalated in separate cohorts from 8mg/kg IV, 12mg/kg IV，16mg/kg IV and 20mg/kg IV. If there is no DLT observe in any of these 3 patients in 7 weeks, then the trial proceeds to enroll 3 patients into the next higher dose cohort. If one subject develops a DLT at a specific cohort, an additional 3 patients are enrolled into that same dose cohort. Development of DLTs in more than 1 of 6 patients in a specific dose cohort suggests that the MTD has been exceeded, and further dose escalation is not pursued. Receives: Drug: Gentuximab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicities (DLT)
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs). A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
Measured: Up to 7 weeks
Pharmacokinetics: Maximum Concentration (Cmax) in single dose
Measured: Cycle 1(day1-day21)& Cycle 2(day 21-day 49): Predose, 15 minute, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours、day 3, day 4, day 7, day 14 after completion of infusion, Cohort 5 only)
Pharmacokinetics: Cmax in multiple dose
Measured: Predose and 15 minutes after completion of Infusion at day 21, day 28, day 42，Predose and 15 minutes, 3 hours, 8 hours, 24 hours, 48 hours, 96 hours after completion of Infusion at day 35，Predose at day 49（the last follow-up）
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) in single dose
Measured: Cycle 1(day1-day 21)& Cycle 2(day 21-day49): up to day 21（blood collection time are as follows ：Predose, 15 minutes, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, day 3, day 4, day 7, day 14 after completion of infusion, Cohort 5 only)
Pharmacokinetics: AUC in multiple dose
Measured: From day 21 up to day 49（blood collection time：Predose and 15 minutes after completion of Infusion at day 21, day 28, day 42，Predose and 15 minutes, 3hours, 8hours, 24hours, 48hours, 96hours after completion of Infusion at day 35，Predose at day 49
Secondary outcomes (4)
Adverse Events
Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
Measured: 4 weeks after disease progression or 4 weeks after the intolerant toxicity occurs or until the subject begins a new tumor treatment (whichever is shorter)
Anti-drug antibody:Number of Participants With Anti-drug Antibodies
A sample will be considered positive for circulating anti-drug antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-drug level seen in healthy untreated individuals. A participant will be considered to have an anti-drug response if there are 2 consecutive positive samples or if the final sample tested is positive.
Measured: Cycle 1（day 1-day 21）: Cycle 2:day 21-day 49, cycle 3：day 50-up to study completion, an average of 2 years
Objective response rate: Number of Participants With Objective Response (ORR)
Participants achieved disease control if they had a BOR of CR, PR or SD. Progressive Disease (PD) and those participants which were Not Evaluable (NE) were also reported. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.
Measured: Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 1 year)
Progression-free survival (PFS)
Defined as the time from randomization to the patient tumor progression or death.
Measured: Time from randomization to the patient tumor progression or death.（up to 1 year）
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start11 Oct 2017
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Changchun GeneScience Pharmaceutical Co., Ltd.The 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changchun GeneScience Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shanghai East Hospital
- Responsible party
- Sponsor
- Investigators
- Jin Li, Principal investigator, Ethics Committee of Drug Clinical Trials
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03313219
- Sponsor's protocol ID
- GenSci 043
- Status last verified
- Oct 2017
- First submitted
- 6 Oct 2017
- Last updated
- 12 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Tolerabilitynce Studies of Gentuximab (Recombinant Anti-VEGFR2 Human-mouse Chimeric Monoclonal Antibody) Injection in the Treatment of Late Recurrence of Metastatic Solid Tumors in China: An Open-label，Non-randomised，Uncontrolled，Dose-escalation，Single Center，Pphase Ia Study in Patients With Late Recurrence of Metastatic Solid Tumors in China
- ClinicalTrials.gov ID
- NCT03313219
- Acronym / sponsor ID
- GenSci 043
- Conditions
- Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Changchun GeneScience Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Shanghai East Hospital
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 18 Oct 2017 (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 primary objective is to evaluate the safety and, tolerabilitytolerance, pharmacokinetices and immunogenicity of escalating single doses and subsequent multiple dose of Gentuximab Injection in patients with late recurrence of metastatic solid tumors and to determine the maximum tolerated dose（MTD） and dose limiting toxicities（DLT）.with single and subsequent multiple intravenous infusion in patients with late recurrence of metastatic solid tumors and to provide a basis for the protocol design of later clinical trials.
The secondary objective is to evaluate the pharmacokinetics, pharmacodynamics and immunogenicity, and tumor response of multiple dose of Gentuximab Injection in patients with late recurrence of metastatic solid tumors.
Detailed description
The safety profile of Gentuximab Injection will be explored together with the pharmacokinetics, pharmacodynamics and tumour response to treatment with Gentuximab Injection to recommend the dosing regimen for further clinical studies. The pharmacokinetic properties of Gentuximab Injection will be evaluated after single and multiple dose administrations at different dose levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gentuximab Injection | Experimental | Drug: Gentuximab InjectionPatients are assigned to a dose level at the time of study entry and scheduled to receive i.v. of a single dose. The patient enter the subsequent multiple dose i.v. in a 7-day cycle if no DLT in 21 days after the first dose. The study period of each subject will be up to 4 cycles until the tumor progression or unacceptable toxicity. The MTD will be determined by assessing DLT in each cohort from cohort 1 to 6, using a 3+3 dose escalation model. Cohort A begin at 4mg/kg IV and the dose escalated in separate cohorts from 8mg/kg IV, 12mg/kg IV，16mg/kg IV and 20mg/kg IV. If there is no DLT observe in any of these 3 patients in 7 weeks, then the trial proceeds to enroll 3 patients into the next higher dose cohort. If one subject develops a DLT at a specific cohort, an additional 3 patients are enrolled into that same dose cohort. Development of DLTs in more than 1 of 6 patients in a specific dose cohort suggests that the MTD has been exceeded, and further dose escalation is not pursued. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Male or female. aged between 18 and 75 years.
- Participants with histopathologically or cytologically diagnosed advanced or metastatic malignant solid tumor.
- Did not respond to standard therapy or no standard therapy is available.
- At least one Measurable lesion.
- At least 4 weeks after the last chemotherapy (at least 14 days from the last medication with oral fluorouracil drugs), at least 6 weeks after the last medication with mitomycin C and nitrosourea; wait for at least a elution periods for 5 half-life if anti-tumor biological products are dosed.
Key exclusion criteria (17 listed)
- Subject who has HIV infection, active hepatitis B, hepatitis C or syphilis infection.
- Subject is histologically confirmed as lung squamous cell carcinoma or squamous cell carcinoma of the head and neck, or subjects with lung metastases and metastases with the void ，or bleeding tendency or risk which researchers conformed.
- Has known alcohol or drug dependency.
- Has participated in a clinical study of a non-approved experimental agent within 4 weeks prior to study entry.
- Have serious infection need antibiotic therapy by intravenous injection .
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 |
|---|---|---|
| Gentuximab InjectionGentuximab Injection (Recombinant anti-VEGFR2 human-mouse chimeric monoclonal antibody injection) | Drug | Gentuximab Injection |
Primary outcome
Dose-limiting toxicities (DLT)
Time frame: Up to 7 weeks
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs). A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
Pharmacokinetics: Maximum Concentration (Cmax) in single dose
Time frame: Cycle 1(day1-day21)& Cycle 2(day 21-day 49): Predose, 15 minute, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours、day 3, day 4, day 7, day 14 after completion of infusion, Cohort 5 only)
Pharmacokinetics: Cmax in multiple dose
Time frame: Predose and 15 minutes after completion of Infusion at day 21, day 28, day 42，Predose and 15 minutes, 3 hours, 8 hours, 24 hours, 48 hours, 96 hours after completion of Infusion at day 35，Predose at day 49（the last follow-up）
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) in single dose
Time frame: Cycle 1(day1-day 21)& Cycle 2(day 21-day49): up to day 21（blood collection time are as follows ：Predose, 15 minutes, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, day 3, day 4, day 7, day 14 after completion of infusion, Cohort 5 only)
Pharmacokinetics: AUC in multiple dose
Time frame: From day 21 up to day 49（blood collection time：Predose and 15 minutes after completion of Infusion at day 21, day 28, day 42，Predose and 15 minutes, 3hours, 8hours, 24hours, 48hours, 96hours after completion of Infusion at day 35，Predose at day 49
4 secondary outcomes
Adverse Events
Time frame: 4 weeks after disease progression or 4 weeks after the intolerant toxicity occurs or until the subject begins a new tumor treatment (whichever is shorter)
Anti-drug antibody:Number of Participants With Anti-drug Antibodies
Time frame: Cycle 1（day 1-day 21）: Cycle 2:day 21-day 49, cycle 3：day 50-up to study completion, an average of 2 years
Objective response rate: Number of Participants With Objective Response (ORR)
Time frame: Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 1 year)
Progression-free survival (PFS)
Time frame: Time from randomization to the patient tumor progression or death.（up to 1 year）
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
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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.
Jin Li principal investigator
Ethics Committee of Drug Clinical Trials
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gentuximab Injection in people with Solid Tumor, run by Changchun GeneScience Pharmaceutical 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 15 inclusion and 17 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 12 Dec 2017. 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 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 Xiaohua Feng (0431-85170552, fengxiaohua@gensci-china.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicities (DLT) (time frame: Up to 7 weeks). The study lists 5 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 12 Dec 2017.