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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• PFS [Срок оценки: Up to 5 years]
• OS [Срок оценки: Up to 5 years]
• Severe drug-related adverse events [Срок оценки: Up to 2 approximately years]

Вторичные конечные точки (7)

• ORR [Срок оценки: Up to 2 approximately years]
• DCR [Срок оценки: Up to 2 approximately years]
• DOR [Срок оценки: Up to 2 approximately years]
• Minor drug-related adverse events [Срок оценки: Up to 2 approximately years]
• Quality-adjusted survival [Срок оценки: Up to 5 years]
• Therapeutic gain [Срок оценки: Up to 2 approximately years]
• Incremental Cost-Effectiveness Ratio (ICER) [Срок оценки: Up to 2 approximately years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT04890522 · B2020-409-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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