Randomized Trial of Loco-regional Radiotherapy Added to Pembrolizumab Alone or With Chemotherapy Versus Systemic Treatment Alone for Patients With Newly Diagnosed Head and Neck Squamous Cell Carcinoma With Synchronous Metastases
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- UNICANCER
- 入组人数
- 102
- 试验地点
- 37
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head & neck cancers
详细描述
Comparative interventional prospective phase 3, randomised, open-label, multicentric trial comparing the combination of radiotherapy and pembrolizumab alone or with chemotherapy to systemic treatment as first line treatment of patients with newly diagnosed head and neck squamous cell carcinoma with synchronous metastases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
- •Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion.
- •Eligible for treatment by pembrolizumab according to the European Marketing Authorization
- •Patient ≥18 years old
- •Performance status: 0-1 (WHO)
- •Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)
- •Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy
- •Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:
- •a. If randomization is done before treatment start: i. Absolute neutrophil count ≥1.5 × 10⁹/L ii. Platelet ≥100 × 10⁹/L iii. Hemoglobin ≥90 g/L iv. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) v. Bilirubin ≤1.5 × ULN. vi. Serum albumin ≥25 g/L vii. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) viii. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L. b. If randomization if done after treatment start i. Absolute neutrophil count ≥1.0 × 10⁹/L ii. Platelet ≥75 × 10⁹/L iii. Hemoglobin ≥85 g/L
- •Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration
- •Patients must be affiliated to a Social Security System (or equivalent)
- •No disease progression during systemic treatment if the randomization is done after the start of pembrolizumab for the current disease
排除标准
- •Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
- •History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma
- •Prior radiotherapy in the head and neck region
- •Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +/- chemotherapy for the current cancer for a maximum of 6 cycles). This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.
- •Known Acquired Immune Deficiency Syndrome (AIDS)
- •Known currently active infection including hepatitis B or hepatitis C
- •Patient having received live attenuated vaccine within 28 days prior to enrolment
- •Pregnant or breast feeding woman
- •Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
- •Active immunodeficiency or ongoing immunosuppressive therapy
- •Active symptomatic interstitial lung disease
- •Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
- •Any social, personal, medical, geographic and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent
- •Prior organ transplantation including allogenic stem-cell transplantation
- •Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- •Person deprived of their liberty or under protective custody or guardianship
- •Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion
研究组 & 干预措施
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity.
Loco-regional radiotherapy(RT) depending on the RT timing :
- Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle.
- After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab.
If the investigator decides before randomization to add chemotherapy and depending on the RT timing:
- Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab.
- RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab.
Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
干预措施: Loco-regional radiotherapy (Radiation)
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity.
Loco-regional radiotherapy(RT) depending on the RT timing :
- Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle.
- After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab.
If the investigator decides before randomization to add chemotherapy and depending on the RT timing:
- Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab.
- RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab.
Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
干预措施: Pembrolizumab (Drug)
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity.
Loco-regional radiotherapy(RT) depending on the RT timing :
- Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle.
- After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab.
If the investigator decides before randomization to add chemotherapy and depending on the RT timing:
- Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab.
- RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab.
Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
干预措施: Chemotherapy (Drug)
Systemic treatment
Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity.
If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin area under the curve (AUC) 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
干预措施: Chemotherapy (Drug)
Systemic treatment
Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity.
If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin area under the curve (AUC) 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: From randomization to disease progression or death, up to 3 years.
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
次要结局
- Overall survival (OS)(From randomization to death from any cause, up to 5 years.)
- Quality of life questionnaire - Core 30 (QLQ-C30)(At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years)
- Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35)(At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years)
- Objective response rate (ORR)(At 18 weeks and 27 weeks)
- Loco-regional progression(From randomization to loco-regional progression, up to 5 years.)
- Distant progression(From randomization to distant progression, up to 5 years.)
- Progression-free survival 2 (PFS2)(Up to 5 years after randomization.)
- Incidence of Treatment Adverse Events(Throughout study completion, up to 5 years.)
- Compliance to treatment(Throughout study treatment, up to 5 years)