An Open-label, Multicentre, Phase II/III RCT of PFLL Versus GP Combined With JS001 as the First-line Therapy for mNPC
- Conditions
- Nasopharyngeal CarcinomaMetastasisImmunotherapyChemotherapySurvival
- Interventions
- Registration Number
- NCT04890522
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
The treatment of distant metastasis is a key challenge for nasopharyngeal carcinoma because of poor outcomes, among which, chemotherapy is the cornerstone. However, many studies reported the use of different chemotherapy regimens to prolong the survival of metastatic nasopharyngeal carcinoma, while few of them focused on how to reduce the side effects of chemotherapy or improve the life quality of patients. Blocking the immune checkpoint is one of the effective strategies of tumor immunotherapy. Thus, we sought to find a proper chemotherapy regimen combined with PD-1 antibody JS001.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 622
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Nasopharyngeal carcinoma diagnosed by pathology or cytology.
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Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) is not amenable for local-regional treatment or curative treatment.
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Has not received prior systemic treatment for metastatic nasopharyngeal carcinoma, except for neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy 6 months prior to the first treatment.
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The Karnofsky performance status score is at least 70 points (if the decreased score is caused by the tumor, the minimum score can be 50 points after the judgment of researchers.)
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Has at least one measurable target lesion based on RECIST v1.1, which is never received local treatment like radiotherapy.
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Life expectancy ≥ 3 months.
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The lab examination results of the screening must fulfill all of the following (use of any blood components, hematopoietic stimulating factors, etc. are not allowed within 14 days before screening):
- absolute neutrophil count ≥1.5×10^9/ L;
- platelet count ≥ 100×10^9/ L;
- hemoglobin ≥ 8.0 g/dL;
- serum albumin ≥ 2.8g/dL;
- aspartate transferase(AST) and alanine transferase(ALT) ≤ 1.5 ×ULN; total bilirubin ≤ 1.5×ULN (if has liver metastasis, AST and ALT ≤ 5×ULN);
- creatinine clearance >50 mL/min.
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Men with reproductive capacity or women of childbearing potential must use highly effective contraceptive methods during the trial (e.g., oral contraceptives, intrauterine device, sexual abstinence or barrier method combined with spermicide), and continue contraception for 3 months after the last injection of JS001 and 6 months after the end of chemotherapy.
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Has signed the Informed Consent Form.
- Allergic to monoclonal antibodies, any JS001 components, gemcitabine, cisplatin, or 5-fluorouracil.
- Has prior therapy including anti-PD-1, anti-PD-L1, or CTLA4.
- Major surgery within 28 days prior to the randomization (not including diagnostic surgery) or plan to be conducted during the study.
- Active autoimmune disease requiring systemic treatment or has a history of autoimmune disease.
- Requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment.
- Allergic to macromolecular protein preparation ingredients.
- Has central nervous system (CNS) metastasis with clinical symptoms.
- Had other invasive malignant diseases, except excised basal-cell skin carcinoma, cervical carcinoma in situ, or other cancers curatively treated more than 5 years before study entry.
- Has cardiac clinical symptoms or disease out of control.
- Has an active infection or unexplained fever with more than 38.5 ℃ during screening and prior to first administration.
- Has acquired or congenital immune-deficient disease, or active hepatitis.
- History of drug abuse or alcohol abuse.
- The investigator judges other factors that may lead to the forced termination of this study, including but not limited to: other serious conditions (including mental disorder) that require concomitant treatment, severe laboratory test abnormalities, family or social factors that may affect the safety of patients or the collection of trial data and samples.
- Pregnancy or breast feeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group Triprilimab(JS001) gemcitabine at a dose of 1,000 mg/m2 by intravenous infusion on days 1, 8, and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1, and intravenous infusion of JS001 240mg on day 1, every 21 days. Experimental group Triprilimab(JS001) 5-fluorouracil intravenous infusion at 200mg/m2/d for 30 continuous days, and intravenous infusion of cisplatin 80 mg/m2 on day 1 and day 28, and intravenous infusion of JS001 240mg on day 1 and day 21, every 60 days. Experimental group Cisplatin 5-fluorouracil intravenous infusion at 200mg/m2/d for 30 continuous days, and intravenous infusion of cisplatin 80 mg/m2 on day 1 and day 28, and intravenous infusion of JS001 240mg on day 1 and day 21, every 60 days. Experimental group 5-Fluorouracil 5-fluorouracil intravenous infusion at 200mg/m2/d for 30 continuous days, and intravenous infusion of cisplatin 80 mg/m2 on day 1 and day 28, and intravenous infusion of JS001 240mg on day 1 and day 21, every 60 days. Control group Cisplatin gemcitabine at a dose of 1,000 mg/m2 by intravenous infusion on days 1, 8, and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1, and intravenous infusion of JS001 240mg on day 1, every 21 days. Control group Gemcitabine gemcitabine at a dose of 1,000 mg/m2 by intravenous infusion on days 1, 8, and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1, and intravenous infusion of JS001 240mg on day 1, every 21 days.
- Primary Outcome Measures
Name Time Method OS Up to 5 years Overall survival
PFS Up to 5 years Progression-free survival
Severe drug-related adverse events Up to 2 approximately years grade III-V according to CTCAE v4.0
- Secondary Outcome Measures
Name Time Method ORR Up to 2 approximately years Objective response rate
DOR Up to 2 approximately years Duration of response
DCR Up to 2 approximately years Disease control rate
Minor drug-related adverse events Up to 2 approximately years grade I-II according to CTCAE v4.0
Quality-adjusted survival Up to 5 years Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment (Q-TWiST), a measure involving the partitioning of survival duration into clinically relevant health states (e.g., treatment toxicity, disease progression, progression-free), assigning preference weights (or utilities) to these health states, and calculating quality of life-adjusted weighted sums of the mean duration of each health state to create the overall Q-TWiST scores.
Therapeutic gain Up to 2 approximately years Calculated by dividing person-year rate of overall survival by person-year rate of serious toxicity.
Incremental Cost-Effectiveness Ratio (ICER) Up to 2 approximately years To estimate the costs and health gains of different interventions, calculated as incremental cost divided by life years gained.
Trial Locations
- Locations (1)
Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China