- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04359550
Study of ZKAB001 for Maintenance Therapy in Patients With High-grade Osteosarcoma After Adjuvant Chemotherapy
A Randomized, Double-blind, Placebo-controlled, Multicenter,Phase III Clinical Study of Recombinant Anti-PD-L1 Monoclonal Antibody (ZKAB001) for Maintenance Therapy in Patients With High-grade Osteosarcoma After Adjuvant Chemotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The patients will be given ZKAB001 injection in 10mg/kg or placebo once every 3 weeks for a total of 16 cycles or 1 year. The end point is that the patient has been taking the drug for 16 cycles or 1 year, or the patient dies or develops intolerable toxicity or confirmed disease recurrence or distant metastasis or withdrawal of informed consent, whichever comes first.
In this study, after a screening period of no more than 28 days, qualified subjects will be given ZKAB001 or placebo and test visits. Imaging examination will be performed every 12 weeks after the first dose until the local or distant recurrence of the disease, or the initiation of other systematic anti-tumor therapy or death, whichever come first.
The survival follow-up period starts from the last treatment to a maximum of 4 years, or to the death or loss of follow-up or withdrawal of informed consent or the sponsor terminates the study every 3 months.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Yang Yao, Master
- Phone Number: 18930177737
- Email: yangyao_6@hotmail.com
Study Contact Backup
- Name: Haiyan Hu, master
- Phone Number: 18930174575
- Email: xuri1104@163.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Voluntarily participate in the trial and sign the informed consent form.
- Age ≥ 12 years old, both male and female.
- High-grade osteosarcoma diagnosed by histopathology (Ennecking stage II) ,radical surgery (R0 resection) and the adjuvant chemotherapy was confirmed by investigators. The end of adjuvant chemotherapy was no more than 12 weeks.
- Chemotherapy with more than two drugs must be used; the accumulated dose of doxorubicin should not be less than 300mg/m^2 (including converted dose); the total course of chemotherapy before and after operation should not be less than 12 times, the starting time of postoperative chemotherapy should not exceed 30 days, and the time of postoperative chemotherapy should not exceed 40 weeks.
- The score of the Eastern Cooperative Oncology Group (ECOG) is 0-1.
- The estimated survival time is more than 3 months.
The functions of important organs meet the following requirements;
- Absolute neutrophil count ≥ 1.5 × 10^9 / L.
- Platelet count ≥ 75 × 10^9 /L.
- Hemoglobin ≥ 90g/L.
- Serum albumin ≥ 28g/L.
- Total bilirubin ≤ 1.5 × ULN;ALT, AST ≤ 2.5 × ULN.
- Serum creatinine ≤ 1.25 × ULN or endogenous creatinine clearance ≥ 50mL/min (using standard Crockcroft-Gault formula).
- Thyroid function: thyroid stimulating hormone (TSH) is normal. If TSH is abnormal, free thyroxine( FT3 and FT4 )levels should be examined. Normal FT3 and FT4 levels can be enrolled.
- Female subjects of childbearing age should take effective contraceptive methods during the study period and within 3 months after the end of the study period, and the serum human chorionic gonadotropin pregnancy test (HCG) must be negative within 7 days before enrollment.
Exclusion Criteria:
- Local recurrence or distant metastasis;
- There is active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, colitis, hepatitis, arthritis, glomerulonephritis, hypophysitis, hyperthyroidism, hypothyroidism, etc.), but does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormones.
- Type I diabetes with stable doses of insulin;
- Vitiligo or cured childhood asthma / allergies in adults without medical intervention.
- The subjects were treated with immunosuppressants, or systemic or absorbable local corticosteroids with the purpose of immunosuppression (prednisone or equivalent for more than 10mg/ days), and continued to use them within 2 weeks before enrollment.
- Have received any form of organ transplantation, including allogeneic stem cell transplantation;
- Previously known to be allergic to macromolecular protein preparations or to any ZKAB001 components;
- Previous or simultaneous suffering from other malignant tumors (except those that have been cured or cancer-free for more than 5 years, such as basal cell carcinoma of the skin, carcinoma in situ of the cervix and papillary carcinoma of the thyroid, etc.);
- Uncontrolled cardiac clinical symptoms or diseases, such as heart failure above New York Heart Association(NYHA) 2, unstable angina pectoris, myocardial infarction within 1 year, clinical supraventricular or ventricular arrhythmias requiring intervention, echocardiography shows that the left ventricular ejection fraction at rest is less than 50%; - The completion of the treatment of radiotherapy, chemotherapy, surgery and/or molecular targeted therapy is less than 3 weeks before the first dose of study drug;
- Active infection (need to be treated with anti-bacterial, viral and/or fungal drugs), or fever of unknown origin occurred during the screening period and occurred within one week before the first dose (judged by the investigators, except the fever caused by tumor).
- Positive for human immunodeficiency virus (HIV); untreated active hepatitis B (hepatitis B surface antigen is positive and peripheral blood HBV-DNA titer ≥ 1000IU/ml or comply with local positive criteria) and/or hepatitis C (hepatitis C antibody is positive and HCV-RNA is higher than the lower limit)
- Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or patients with active pulmonary tuberculosis infection within one year before entering the group, or patients with active pulmonary tuberculosis infection history more than one year ago but without formal treatment;
- Participating in other clinical studies, or less than 4 weeks from the end of the previous clinical study;
- Other systemic anti-tumor therapy may be received during the study period;
- Previously received other PD-1 and / or PD-L1, or CTLA-4 antibody therapy, or other drug therapy for immune receptor modulators;
- The live vaccine was vaccinated within 4 weeks before screening.
- Known history of psychotropic substance abuse, alcohol abuse or drug use;
- Pregnant or lactating women;
- Any mental state that hinders the understanding or provision of informed consent;
- The investigators consider that the patient had other factors that might lead to the termination of the study, such as other serious diseases or serious laboratory abnormalities or accompanied by other factors that would affect the safety of the subjects, or family or social factors that would affect the collection of data and samples.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: treatment group
ZKAB001 injection 10mg/kg once every 3 weeks for 1 cycle (Q3w), up to 16 cycles or 1 year of treatment.
|
Recombinant human anti-PD-L1 monoclonal antibody (ZKAB001)
|
Placebo Comparator: control group
placebo will given in the same way for once every 3 weeks for 1 cycle (Q3w), up to 16 cycles or 1 year of treatment.
|
placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
One-year DFS rate
Time Frame: 1 year
|
The percentage of patients with no recurrence or metastasis within one year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Five-years OS rate
Time Frame: 5 years
|
Patients who survive within 5 years after the first dose.
|
5 years
|
adverse events
Time Frame: 5 years
|
Incidence and severity of adverse events
|
5 years
|
Immunogenecity of ZKAB001
Time Frame: 1 year
|
To evaluated the number of subjects presenting detectable anti drug antibodies (ADAs).
|
1 year
|
PD-L1 expression
Time Frame: 1 year
|
Correlation between PD-L1 expression level and clinical efficacy
|
1 year
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NTL-LEES-2019-08
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on High-grade Osteosarcoma
-
Klinikum StuttgartKlinikum Kassel GmbH (COSS-Biobank)Not yet recruitingOsteosarcoma | High Grade Sarcoma | Recurrent Osteosarcoma | Bone Sarcoma | Undifferentiated Pleomorphic Sarcoma | Bone Tumor | Extraskeletal Osteosarcoma | Osseous Sarcoma | Parosteal Osteosarcoma | Osteoblastic Osteosarcoma | Chondroblastic Osteosarcoma | Fibroblastic Osteosarcoma | Conventional Osteosarcoma | Conventional... and other conditions
-
National Cancer Institute (NCI)SuspendedMetastatic Osteosarcoma | Localized Osteosarcoma | High Grade Osteosarcoma | Secondary OsteosarcomaUnited States
-
Grupo de Apoio ao Adolescente e a Crianca com CancerUnknown
-
Gustave Roussy, Cancer Campus, Grand ParisCompletedOsteosarcoma | Localised High Grade Osteosarcoma of the LimbsFrance
-
Assistance Publique - Hôpitaux de ParisRecruiting
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedHigh Grade Anal Canal Intraepithelial Neoplasia | High Grade Vulvar Squamous Intraepithelial LesionUnited States
-
M.D. Anderson Cancer CenterRecruitingRecurrent Primary Peritoneal High Grade Serous Adenocarcinoma | High Grade Ovarian Serous Adenocarcinoma | Recurrent High Grade Fallopian Tube Serous Adenocarcinoma | Recurrent High Grade Ovarian Serous Adenocarcinoma | High Grade Fallopian Tube Serous Adenocarcinoma | Peritoneal High Grade...United States
-
Andrew J. GunnPenumbra Inc.Recruiting
-
Poitiers University HospitalCompleted
-
Gruppo Italiano Studio LinfomiCompleted
Clinical Trials on placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States