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

NCT04890522 | Not Yet Recruiting Phase 2

• 1 other identifier: B2020-409-01
• Study Type: interventional
• Target: 622
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Carcinoma; Metastasis; Chemotherapy; Immunotherapy; Survival

Outcome Measures

Primary Outcomes (3)

• PFS

  Progression-free survival

  Up to 5 years

• OS

  Overall survival

  Up to 5 years

• Severe drug-related adverse events

  grade III-V according to CTCAE v4.0

  Up to 2 approximately years

Secondary Outcomes (7)

• ORR

  Up to 2 approximately years

• DCR

  Up to 2 approximately years

• DOR

  Up to 2 approximately years

• Minor drug-related adverse events

  Up to 2 approximately years

• Quality-adjusted survival

  Up to 5 years

Study Arms (2)

Experimental group

EXPERIMENTAL

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: Triprilimab(JS001); Drug: Cisplatin; Drug: 5-Fluorouracil

Control group

ACTIVE COMPARATOR

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: Triprilimab(JS001); Drug: Cisplatin; Drug: Gemcitabine

Interventions

Triprilimab(JS001) DRUG

Maximum 6 cycles for combined therapy and maintenance for up to 2 years.

Control group; Experimental group

Cisplatin DRUG

Maximum 6 cycles for combined therapy.

Control group; Experimental group

5-Fluorouracil DRUG

Maximum 6 cycles for combined therapy.

Experimental group

Gemcitabine DRUG

Maximum 6 cycles for combined therapy.

Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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):
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Department of Radiation Oncology, Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Neoplasm Metastasis

Interventions

Cisplatin; Fluorouracil; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Study Officials

• Yun-fei Xia, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun-fei Xia, MD

CONTACT

+8613602805461; xiayf@sysucc.org.cn

Shuohan Zheng, MD

CONTACT

+8613826478924; zhengsh1@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 18, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2023
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)