An Open-label, Multicentre, Phase II/III RCT of PFLL Versus GP Combined With JS001 as the First-line Therapy for mNPC

A Randomized, Open-label, Multicentre, Phase II/III Study of Low-dose Long-term Continuous Intravenous Infused 5-fluorouracil Versus Gemcitabine Combined With Cisplatin and JS001 as First-line Therapy for Metastatic Nasopharyngeal Carcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma; Chemotherapy; Metastasis; Immunotherapy; Survival
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Triprilimab(JS001); Drug: 5-Fluorouracil

• Study Type: Interventional
• Enrollment (Anticipated): 622
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Shuohan Zheng, MD; Phone Number: +8613826478924; Email: zhengsh1@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
      • Contact: Shuohan Zheng, MD; Phone Number: +8613826478924; Email: zhengsh1@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Nasopharyngeal carcinoma diagnosed by pathology or cytology.
• 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.
• 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.
• 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.)
• Has at least one measurable target lesion based on RECIST v1.1, which is never received local treatment like radiotherapy.
• Life expectancy ≥ 3 months.

• 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):

  1. absolute neutrophil count ≥1.5×10^9/ L;
  2. platelet count ≥ 100×10^9/ L;
  3. hemoglobin ≥ 8.0 g/dL;
  4. serum albumin ≥ 2.8g/dL;
  5. aspartate transferase(AST) and alanine transferase(ALT) ≤ 1.5 ×ULN; total bilirubin ≤ 1.5×ULN (if has liver metastasis, AST and ALT ≤ 5×ULN);
  6. creatinine clearance >50 mL/min.
• 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.
• Has signed the Informed Consent Form.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; 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.	Drug: Cisplatin; Maximum 6 cycles for combined therapy.; Drug: Triprilimab(JS001); Maximum 6 cycles for combined therapy and maintenance for up to 2 years.; Drug: 5-Fluorouracil; Maximum 6 cycles for combined therapy.
Active Comparator: Control group; 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.	Drug: Gemcitabine; Maximum 6 cycles for combined therapy.; Drug: Cisplatin; Maximum 6 cycles for combined therapy.; Drug: Triprilimab(JS001); Maximum 6 cycles for combined therapy and maintenance for up to 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival	Up to 5 years
Severe drug-related adverse events	grade III-V according to CTCAE v4.0	Up to 2 approximately years
OS	Overall survival	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate	Up to 2 approximately years
DCR	Disease control rate	Up to 2 approximately years
DOR	Duration of response	Up to 2 approximately years
Minor drug-related adverse events	grade I-II according to CTCAE v4.0	Up to 2 approximately years
Quality-adjusted survival	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.	Up to 5 years
Therapeutic gain	Calculated by dividing person-year rate of overall survival by person-year rate of serious toxicity.	Up to 2 approximately years
Incremental Cost-Effectiveness Ratio (ICER)	To estimate the costs and health gains of different interventions, calculated as incremental cost divided by life years gained.	Up to 2 approximately years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 16, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 16, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Fluorouracil
• Other Study ID Numbers: B2020-409-01

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
• product manufactured in and exported from the U.S.: No