- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03167853
Study of JS001 in Patients With Advanced Neuroendocrine Tumors
June 20, 2019 updated by: Shen Lin, Peking University
Phase Ib Study of Safety and Efficacy of Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Patients With Advanced Neuroendocrine Tumors Following Failure of First-Line
This is a multi-center, open-label, phase Ib study evaluating safety and efficacy of the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with neuroendocrine tumors who have failed in previous systemic treatment.
40 patients are enrolled and injected with the humanized anti-PD-1 antibody 3mg/mg every 2 weeks until disease progresses or unacceptable toxicity.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Beijing
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Beijing, Beijing, China, 100142
- Beijing Cancer Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
- Male and Female aged 18 and older are eligible;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- Histologic diagnosis of locally advanced or metastatic nonfunctional neuroendocrine tumors, including well-differentiated neuroendocrine tumors and pooly-differentiated neuroendocrine carcinoma;
- Ki-67 index ≥10%;
- Unresectable;
- Radiographic evidence of disease rogression by RECIST criteria on or after last anti-cancer therapy within 6 months;
Prior treatment meeting the following criteria:
- Patients with pooly-differentiated neuroendocrine carcinomas must have received platinum based lineds of chemotherapy;
- Patients with well-differentiated neuroendocrine tumors must have received at least one systemic treatment, including somatostatin analogs, mTOR inhibitors, anti-angiogentic agents and chemotherapy;
- Providing with tumor specimen (for testing the expression of PD L1 and the infiltrating lymphocytes);
- Predicted survival >=3 months;
- At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan >=20mm, spiral CT scan >=10mm, no prior radiation to measurable lesions);
- Screening laboratory values must meet the following criteria (within past 14 days): hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ μL; platelets ≥ 100 x 10^3/ μL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1╳ULN, creatinine clearance >50ml/min (CockcroftGault equation) PT/INR, aPTT≤1.5 x ULN;
- Without systemic steroids within past 4 weeks;
- Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (prior systemic steroids was allowed, but concurrent administration of systemic steroids with the study drug is excluded);
- Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
Exclusion Criteria:
- Prior treatment with antiPD1/PDL1/PDL2 antibody;
- Hypersensitivity to recombinant humanized antiPD1 monoclonal Ab or its components;
- Prior treatment with mAb within past 4 weeks;
- Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
- Pregnant or nursing;
- Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml);
- History with tuberculosis;
- Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
- Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II NYHA, heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm);
- Evidence with active CNS disease;
- Meningeal carcinomatosis;
- Prior treatment with bone marrow stimulating factors,such as CSF (colony stimulating factor), EPO (erythropoietin), within past 2 weeks;
- Prior live vaccine therapy within past 4 weeks;
- Prior major surgery within past 4 weeks (diagnostic surgery excluded);
- Psychiatric medicines abuse without withdrawal, or history of psychiatric illness;
- Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix;
- Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: humanized anti-PD-1 monoclonal antibody
humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg per 2 weeks until disease progresses or unacceptable tolerability occurs.
|
humanized anti-PD-1 monoclonal antibody(JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with th combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activitation of lymphocytes and elimination of malignancy theoretically.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
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CT/MRI will be performed every 2 cycles of treatment by RECIST 1.1(each cycle is 21 days))
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From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival
Time Frame: baseline, every 8 weeks up to 1 year after last patient first treatment
|
Progression-free survival is defined as the time from the date of first dose to the date of the first documented radiological progression or death due to any cause
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baseline, every 8 weeks up to 1 year after last patient first treatment
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Duration of response (DOR)
Time Frame: baseline, every 8 weeks up to 1 year after last patient first treatment
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Duration of Response by irRC and RECIST 1.1
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baseline, every 8 weeks up to 1 year after last patient first treatment
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Overall survival
Time Frame: Every 3 months after last visit up to 2 year after last patient first treatment
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Overall survival is defined as the time from date of start of treatment to date of death due to any cause
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Every 3 months after last visit up to 2 year after last patient first treatment
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Immune Response Criteria by irRECIST (immune response duration of response)
Time Frame: baseline, every 8 weeks up to 1 year after last patient first treatment
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Immune Response Criteria by irRECIST and as per BIRC (immune response duration of response)
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baseline, every 8 weeks up to 1 year after last patient first treatment
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Immune Response Criteria by irRECIST (immune response overall response rate)
Time Frame: baseline, every 8 weeks up to 1 year after last patient first treatment
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Immune Response Criteria by irRECIST and as per BIRC (immune response overall response rate)
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baseline, every 8 weeks up to 1 year after last patient first treatment
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Biochemical response
Time Frame: baseline, 6th week, 16th week
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Changes from baseline in chromogranin-A
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baseline, 6th week, 16th week
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Correlation analysis of PD-L1/CD8 expression of tumor and ORR
Time Frame: 3 years
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Changes from baseline in PD-L1/CD8 expression
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3 years
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Correlation analysis of circulating tumor cells (CTC) and ORR
Time Frame: baseline, 8th week
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Changes from baseline of circulating tumor cells (CTC)
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baseline, 8th week
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
April 6, 2017
Primary Completion (ACTUAL)
December 11, 2018
Study Completion (ACTUAL)
May 11, 2019
Study Registration Dates
First Submitted
May 10, 2017
First Submitted That Met QC Criteria
May 24, 2017
First Posted (ACTUAL)
May 30, 2017
Study Record Updates
Last Update Posted (ACTUAL)
June 21, 2019
Last Update Submitted That Met QC Criteria
June 20, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HMO-JS001-Ib-NEC-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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.
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