A Randomised, Open-label, Phase III Study to Evaluate the Efficacy and Safety of Oral Afatinib (BIBW 2992) Versus Intravenous Methotrexate in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Who Have Progressed After Platinum-based Therapy.
概览
- 阶段
- 3 期
- 干预措施
- Afatinib
- 疾病 / 适应症
- Head and Neck Neoplasms
- 发起方
- Boehringer Ingelheim
- 入组人数
- 340
- 试验地点
- 83
- 主要终点
- Progression Free Survival (PFS)
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
This randomized, open-label, phase III study will be performed in patients with recurrent and/or metastatic head and neck cancer which has progressed after platinum-based therapy. The objectives of this trial are to compare the efficacy and safety of afatinib versus methotrexate.
研究者
入排标准
入选标准
- •Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy.
- •Documented progressive disease based on investigator assessment according to RECIST, following receipt of a cisplatin and/or carboplatin and/or Nedaplatin based regimen administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy.
- •Measurable disease according to RECIST (version 1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Visit
- •Male and female patients age is 18 years or older
- •Signed and dated written informed consent that is in compliance with ICH-GCP and local law.
排除标准
- •Progressive disease within three months after completion of curatively intended treatment for locoregionally advanced or for metastatic head and neck squamous cell cancer (HNSCC).
- •Primary tumour site nasopharynx (of any histology), sinuses, and/or salivary glands.
- •Any other than one previous platinum based systemic regimen given for recurrent and/or metastatic disease, with the exception of immunotherapy used either before or after platinum based treatment. Re-challenge with the platinum based regimen after a temporary break is considered an additional line regimen only in case of progression within the break.
- •Prior treatment with EGFR-targeted small molecules.
- •Treatment with any investigational drug less than four weeks or anti-cancer therapy less than three weeks prior to randomization (except palliative radiotherapy to bones to alleviate pain).
- •Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade \>2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade \>1 and/or diarrhoea CTCAE grade \>1 caused by prior treatment with EGFR targeted antibodies.
- •Previous tumour bleeding CTCAE grade =
- •Requirement for treatment with any of the prohibited concomitant medications.
- •Major surgical or planned procedure less than four weeks prior to randomization (isolated biopsies are not considered as major surgical procedures).
- •Any other malignancy unless free of disease for at least five years except for:
研究组 & 干预措施
Afatinib 40 mg
Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after being treated with platinum-based therapy took, orally, once daily one film-coated tablet of afatinib. Patients started with a 40 milligrams (mg) dose which could be escalated to 50 mg and/or reduced to 40 mg, 30 mg, or 20 mg, according to the absence of presence of drug-related adverse events (AEs).
干预措施: Afatinib
Methotrexate 40 mg
Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after being treated with platinum-based therapy received once weekly an intravenous bolus injection of methotrexate. Patients started with a 40 milligrams (mg) per square meter of body surface area (m\^2) dose which could be escalated to 50 mg/m\^2 and/or reduced to 40 mg/m\^2, 30 mg/m\^2, or 20 mg/m\^2, according to the absence of presence of drug-related adverse events (AEs).
干预措施: Methotrexate
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From randomization until disease progression, death, or primary completion date, whichever occurs first. Up to 35 months.
Progression-free survival (PFS) was defined as the time from the date of randomization to the date of disease progression (PD) evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1). or to the date of death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier curves generated for each group.
次要结局
- Objective Response (OR)(From randomization until earliest of disease progression, death, or interim cut-off date (11-Apr-2019). Up to 35 months.)
- Overall Survival (OS)(From randomization until death. Up to 6 years.)
- Time to Deterioration in Global Health Status(From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 30 months.)
- Time to Deterioration in Pain Symptoms(From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 19 months.)
- Time to Deterioration in Swallowing(From randomization until the earliest of deterioration, death, discontinuation with death within 4 weeks, or primary analysis date. Up to 19 months.)
- Change in Global Health Status Over Time(Mean change over time is reported up to 12 weeks. Detailed time frame in the endpoint description.)
- Change in Pain Scale Score Over Time(Mean change over time is reported up to 12 weeks. Detailed time frame in the endpoint description.)
- Change in Swallowing Scale Scores Over Time(Mean change over time is reported up to 12 weeks. Detailed time frame in the endpoint description.)
- Number of Participants With Improvement in Pain Scale Score(Up to 37 months.)
- Number of Participants With Improvement in Swallowing Scale Score(Up to 37 months.)
- Number of Participants With Improvement in Overall Health Rate of the Global Health Status(Up to 37 months.)
- Number of Participants With Improvement in Quality of Life Rate of the Global Health Status(Up to 37 months.)