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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04890522
• Other study ID #: B2020-409-01
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: July 1, 2021
• Est. completion date: December 31, 2028

Study information

• Verified date: May 2021
• Source: Sun Yat-sen University
• Contact: Yun-fei Xia, MD
• Phone: +8613602805461
• Email: xiayf[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 622
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapy
• Immunotherapy
• Metastasis
• Nasopharyngeal Carcinoma
• Survival

Intervention

Drug:
• Triprilimab(JS001)
Maximum 6 cycles for combined therapy and maintenance for up to 2 years.
• Cisplatin
Maximum 6 cycles for combined therapy.
• 5-Fluorouracil
Maximum 6 cycles for combined therapy.
• Gemcitabine
Maximum 6 cycles for combined therapy.

Locations

Country	Name	City	State
China	Department of Radiation Oncology, Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	Progression-free survival	Up to 5 years
Primary	OS	Overall survival	Up to 5 years
Primary	Severe drug-related adverse events	grade III-V according to CTCAE v4.0	Up to 2 approximately years
Secondary	ORR	Objective response rate	Up to 2 approximately years
Secondary	DCR	Disease control rate	Up to 2 approximately years
Secondary	DOR	Duration of response	Up to 2 approximately years
Secondary	Minor drug-related adverse events	grade I-II according to CTCAE v4.0	Up to 2 approximately years
Secondary	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
Secondary	Therapeutic gain	Calculated by dividing person-year rate of overall survival by person-year rate of serious toxicity.	Up to 2 approximately years
Secondary	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