Clinical trial NCT04890522: An Open-label, Multicentre, Phase II/III RCT of PFLL Versus GP Combined With JS001 as the First-line Therapy for mNPC
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Nasopharyngeal Carcinoma
Metastasis
Chemotherapy
Immunotherapy
Survival
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Shanghai Junshi Bioscience Co., Ltd.
First posted: 2021-05-18
Enrollment: 622
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: PFS
timeFrame: Up to 5 years
measure: OS
timeFrame: Up to 5 years
measure: Severe drug-related adverse events
timeFrame: Up to 2 approximately years
Secondary outcomes:
measure: ORR
timeFrame: Up to 2 approximately years
measure: DCR
timeFrame: Up to 2 approximately years
measure: DOR
timeFrame: Up to 2 approximately years
measure: Minor drug-related adverse events
timeFrame: Up to 2 approximately years
measure: Quality-adjusted survival
timeFrame: Up to 5 years
measure: Therapeutic gain
timeFrame: Up to 2 approximately years
measure: Incremental Cost-Effectiveness Ratio (ICER)
timeFrame: Up to 2 approximately years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yun-fei Xia, MD
role: PRINCIPAL_INVESTIGATOR
References: