Study of ZKAB001 for Maintenance Therapy in Patients With High-grade Osteosarcoma After Adjuvant Chemotherapy

NCT04359550 | Unknown Phase 3 DMC

• 1 other identifier: NTL-LEES-2019-08
• Study Type: interventional
• Target: 362
• Locations: 0 countries
• Sites: N/A

Brief Summary

It is a randomized, double-blind, placebo-controlled, multicenter study with the sample size is 362. The patients with high-grade osteosarcoma who had previously received surgery and completed adjuvant chemotherapy will be randomly assigned to ZKAB001 group (trial group) or placebo group (control group) according to 1:1. The purpose is to evaluate the efficacy and safety of ZKAB001 in maintenance therapy after adjuvant chemotherapy in patients with high-grade osteosarcoma.

Conditions

High-grade Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• One-year DFS rate

  The percentage of patients with no recurrence or metastasis within one year

  1 year

Secondary Outcomes (4)

• Five-years OS rate

  5 years

• adverse events

  5 years

• Immunogenecity of ZKAB001

  1 year

• PD-L1 expression

  1 year

Study Arms (2)

treatment group

EXPERIMENTAL

ZKAB001 injection 10mg/kg once every 3 weeks for 1 cycle (Q3w), up to 16 cycles or 1 year of treatment.

Biological: Recombinant human anti-PD-L1 monoclonal antibody (ZKAB001)

control group

PLACEBO COMPARATOR

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.

Other: placebo

Interventions

Recombinant human anti-PD-L1 monoclonal antibody (ZKAB001) BIOLOGICAL

Recombinant human anti-PD-L1 monoclonal antibody (ZKAB001)

treatment group

placebo OTHER

placebo

control group

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Central Study Contacts

Yang Yao, Master

CONTACT

18930177737; yangyao_6@hotmail.com

Haiyan Hu, master

CONTACT

18930174575; xuri1104@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: June 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: April 29, 2020

Record last verified: 2020-04