OsteosarcomaPhase 1/2NCT03676985
A Clinical Study of PD-L1 Antibody ZKAB001(Drug Code) in Limited Stage of High-grade Osteosarcoma
A Phase 1/2 study testing ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Osteosarcoma, run by Lee's Pharmaceutical Limited at 1 site in China.
Trial summary
This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system)… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 10 Oct 2018to 23 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- The patient voluntarily gives written informed consent to participate in the study.
- Patients aged between 18 and 55 (inclusive).
- To diagnosed with limited stage of high-grade osteosarcoma (AJCC stage I-III) by histologically, the patients must have received neoadjuvant chemotherapy and adjuvant chemotherapy and primary tumor radical surgery (R0). The end of adjuvant chemotherapy should less than 12 weeks. Chemotherapy regimens must contain doxorubicin (ADM)/epirubicin (EPI)/pirarubicin (THP)/doxorubicin liposome (PLD) and cisplatin (DDP), the minimum cumulative doses are ADM 360 mg/m2, EPI 450mg/m2, THP 300mg/m2, PLD 240 mg/m2 and DDP 480 mg/m2.
- Eastern Cooperative Oncology Group（ECOG）performance status of 0 or 1, with estimated life expectancy of at least 3 months.
- Adequate blood routine, hepatic and renal function:
- 1)neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN（upper limit of normal）; 6)Alanine transaminase （ALT）and AST≤1.5 x ULN, serum Cr≤1.25 x ULN; 7) endogenous creatinine clearance≥50 ml/min (according Gault Cockcroft formula).
- 7.Female reproductive subjects should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin（HCG） examination must be negative within 7 days before the subject is enrolled.
Who cannot join
- Local recurrence or metastasis.
- Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, adult still need medical intervention; Patients need bronchodilators for medical intervention of asthma.
- Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
- Have received any form of organ transplantation, including allogeneic stem cell transplantation.
- Known allergy to macromolecular protein inhibitors or any of the components of ZKAB001.
- Suffering from other malignant tumors other than this diseases in 5 years except for skin basal cell and squamous cell carcinoma.
Show all 19Show fewer
- Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose >10mg/day prednisone or equivalent) less than 2 weeks.
- Patients with clinical symptoms or diseases of the heart that cannot be well controlled, such as heart failure above New York Heart Association（NYHA ）2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, have left ventricular ejection fraction < 50% at rest in the ultrasound cardiogram.
- Previous radiotherapy, chemotherapy, surgery or molecular targeted therapy, less than 3 weeks after treatment and before study drug; Patients whose adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
- Active infection, or unexplained fever> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
- Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
- The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
- To receive other anti-tumor treatment during the study.
- To treated with other PD-1 and/or PD-1, or CTLA-4（Cytotoxic T Lymphocyte Antigen-4）antibodies, or other drugs for immunomodulatory receptor preparations previously.
- Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus（HPV）vaccine) within 28 days before screening.
- History of mental drug abuse, alcohol abuse or drug abuse.
- Pregnant or lactating women.
- Any mental condition that prevents the understanding or provision of the informed consent.
- It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the patients , family or social factors that may affect the study data and sample collection.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Sixth People's Hospital
Shanghai, Shanghai Municipality, 200233
yang Yao, master
About this study
Official title: An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Limited Stage of High-grade Osteosarcoma of Maintenance Therapy After Adjuvant Chemotherapy
This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with limited stage of high-grade osteosarcoma of maintenance therapy after adjuvant chemotherapy.
Read the detailed description
The study will consist of 4 periods: Screening (up to 28 days), Lead-in period (Day -28), Treatment (up to 24 cycles or 1 year, whichever occurs first), and Follow-up (up to 2 years). There will be a lead-in period on Day -28 for each dose escalation cohort in which the single-dose pharmacokinetics(PK) of ZKAB001 will be characterized prior to initiation of continuous dosing in the first cycle of treatment. The lead-in period duration, PK time-points, doses and/or regimens used in subsequent cohorts may be modified based on the exposure (AUC) observed during the lead-in period (although the number of PK samples will not be increased). Treatment of continuous dosing is up to 24 cycles or 1 year, until as per investigator's opinion, subjects experience disease progression (evaluated by RECIST 1.1), no clinical benefit, or intolerable toxicity. If investigators suspect subjects experience pseudoprogression or has evidence to prove "mixed response", subjects can continue to accept treatment as investigator decided.
- Conditions
- Osteosarcoma
- Being tested
- ZKAB001 5mg/kg, ZKAB001 10mg/kg, ZKAB001 15mg/kg
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZKAB001 5mg/kgDrug
Also called PD-L1 monoclonal antibody
5mg/kg/times bi-week IV administration of ZKAB001
ZKAB001 10mg/kgDrug
Also called PD-L1 monoclonal antibody
10mg/kg/times bi-week IV administration of ZKAB001
ZKAB001 15mg/kgDrug
Also called PD-L1 monoclonal antibody
15mg/kg/times bi-week IV administration of ZKAB001
| Study group | Role | What they receive |
|---|---|---|
| ZKAB001 5 mg/kg/time | Experimental | Three or six patients will treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. Receives: Drug: ZKAB001 5mg/kg |
| ZKAB001 10 mg/kg/time | Experimental | Three or six patients will treated with the dose of 10 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. Receives: Drug: ZKAB001 10mg/kg |
| ZKAB001 15 mg/kg/time | Experimental | Three or six patients will treated with the dose of 15 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. Receives: Drug: ZKAB001 15mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT)
Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.
Measured: 28 days after first dose
Secondary outcomes (12)
Maximal tolerable dose(MTD)
DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.
Measured: 28 days after first dose
EFS(event-free survival)
The rate of 3-year event-free survival
Measured: through study completion, an average of 3 years
AUC(0-t)
Area under curve 0-t
Measured: 24 periods or 1 year
AUC(INF)
Area under curve INF
Measured: 24 periods or 1 year
Cmax
Peak concentration
Measured: 24 periods or 1 year
Tmax
Peak time
Measured: 24 periods or 1 year
T1/2
Half life
Measured: 24 periods or 1 year
Vss
Steady-state apparent volume of distribution based on plasma concentration
Measured: 24 periods or 1 year
total body clearance（CLT）
total body clearance
Measured: 24 periods or 1 year
Cmin
The trough value at steady state
Measured: 24 periods or 1 year
the percentage of the receptors of PD-L1 in CD14+ monocytes and CD3+T cells
To detected the percentage of the receptors of PD-L1 in CD14+（cluster of differentiation 14+ ） monocytes and CD3+（cluster of differentiation 3+）T cells.
Measured: through study completion, an average of 3 years
the number of subjects presenting detectable anti drug antibodies (ADAs)
To evaluated the number of subjects presenting detectable anti drug antibodies (ADAs).
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start10 Oct 2018 (estimated)
- Primary completion14 Feb 2020 (estimated)
- Study completion23 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteosarcomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lee's Pharmaceutical Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- yang Yao, master, Study director, 600 yishan road, Shanghai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03676985
- Sponsor's protocol ID
- NTL-LEES-2017-03
- Status last verified
- Sep 2018
- First submitted
- 13 Sep 2018
- Last updated
- 26 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Limited Stage of High-grade Osteosarcoma of Maintenance Therapy After Adjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT03676985
- Acronym / sponsor ID
- NTL-LEES-2017-03
- Conditions
- Osteosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Lee's Pharmaceutical LimitedIndustry (pharma, biotech, devices)
- Study start
- 10 Oct 2018 (estimated)
- Primary completion
- 14 Feb 2020 (estimated)
- Study completion
- 23 Jun 2023 (estimated)
- First posted
- 19 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with limited stage of high-grade osteosarcoma of maintenance therapy after adjuvant chemotherapy.
Detailed description
The study will consist of 4 periods: Screening (up to 28 days), Lead-in period (Day -28), Treatment (up to 24 cycles or 1 year, whichever occurs first), and Follow-up (up to 2 years). There will be a lead-in period on Day -28 for each dose escalation cohort in which the single-dose pharmacokinetics(PK) of ZKAB001 will be characterized prior to initiation of continuous dosing in the first cycle of treatment. The lead-in period duration, PK time-points, doses and/or regimens used in subsequent cohorts may be modified based on the exposure (AUC) observed during the lead-in period (although the number of PK samples will not be increased). Treatment of continuous dosing is up to 24 cycles or 1 year, until as per investigator's opinion, subjects experience disease progression (evaluated by RECIST 1.1), no clinical benefit, or intolerable toxicity. If investigators suspect subjects experience pseudoprogression or has evidence to prove "mixed response", subjects can continue to accept treatment as investigator decided.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ZKAB001 5 mg/kg/time | Experimental | Drug: ZKAB001 5mg/kgThree or six patients will treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. |
| ZKAB001 10 mg/kg/time | Experimental | Drug: ZKAB001 10mg/kgThree or six patients will treated with the dose of 10 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. |
| ZKAB001 15 mg/kg/time | Experimental | Drug: ZKAB001 15mg/kgThree or six patients will treated with the dose of 15 mg/kg/time of ZKAB001 IV bi-weekly. DLT was observed within 28 days after administration. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- The patient voluntarily gives written informed consent to participate in the study.
- Patients aged between 18 and 55 (inclusive).
- To diagnosed with limited stage of high-grade osteosarcoma (AJCC stage I-III) by histologically, the patients must have received neoadjuvant chemotherapy and adjuvant chemotherapy and primary tumor radical surgery (R0). The end of adjuvant chemotherapy should less than 12 weeks. Chemotherapy regimens must contain doxorubicin (ADM)/epirubicin (EPI)/pirarubicin (THP)/doxorubicin liposome (PLD) and cisplatin (DDP), the minimum cumulative doses are ADM 360 mg/m2, EPI 450mg/m2, THP 300mg/m2, PLD 240 mg/m2 and DDP 480 mg/m2.
- Eastern Cooperative Oncology Group（ECOG）performance status of 0 or 1, with estimated life expectancy of at least 3 months.
- Adequate blood routine, hepatic and renal function:
Key exclusion criteria (19 listed)
- Local recurrence or metastasis.
- Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, adult still need medical intervention; Patients need bronchodilators for medical intervention of asthma.
- Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
- Have received any form of organ transplantation, including allogeneic stem cell transplantation.
- Known allergy to macromolecular protein inhibitors or any of the components of ZKAB001.
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 |
|---|---|---|
| ZKAB001 5mg/kgAlso: PD-L1 monoclonal antibody5mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 5 mg/kg/time |
| ZKAB001 10mg/kgAlso: PD-L1 monoclonal antibody10mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 10 mg/kg/time |
| ZKAB001 15mg/kgAlso: PD-L1 monoclonal antibody15mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 15 mg/kg/time |
Primary outcome
Dose limiting toxicity (DLT)
Time frame: 28 days after first dose
Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.
12 secondary outcomes
Maximal tolerable dose(MTD)
Time frame: 28 days after first dose
EFS(event-free survival)
Time frame: through study completion, an average of 3 years
AUC(0-t)
Time frame: 24 periods or 1 year
AUC(INF)
Time frame: 24 periods or 1 year
Cmax
Time frame: 24 periods or 1 year
Tmax
Time frame: 24 periods or 1 year
T1/2
Time frame: 24 periods or 1 year
Vss
Time frame: 24 periods or 1 year
total body clearance（CLT）
Time frame: 24 periods or 1 year
Cmin
Time frame: 24 periods or 1 year
the percentage of the receptors of PD-L1 in CD14+ monocytes and CD3+T cells
Time frame: through study completion, an average of 3 years
the number of subjects presenting detectable anti drug antibodies (ADAs)
Time frame: through study completion, an average of 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2018.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
Related trials for Osteosarcoma
RecruitingPhase 1/2
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma
RecruitingObservational study
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
RecruitingPhase 2
Iscador® P (Mistletoe) Immunotherapy for Recurrent Resectable Osteogenic Sarcoma
Osteogenic Sarcoma Recurrent
RecruitingPhase 2
The CATSINDO Trial - Clinical and Translational Study in Newly Diagnosed Osteosarcoma
Osteosarcoma in Children, Osteosarcoma in Adolescents and Young Adults
RecruitingPhase 2
Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma
Pediatric Osteosarcoma
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.
yang Yao, master study director
600 yishan road, Shanghai
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 ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Osteosarcoma, run by Lee's Pharmaceutical Limited 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 7 inclusion and 19 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 26 Sep 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact yang Yao, master (18930177737, yangyao_6@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) (time frame: 28 days after first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03676985, which also lists 1 linked publication.
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 26 Sep 2018.