A Randomized, Placebo-Controlled, Phase 2 Study of Docetaxel and Cisplatin/Carboplatin With or Without Erlotinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 5
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This randomized phase II trial studies how well combination chemotherapy with or without erlotinib hydrochloride works in treating patients with squamous cell carcinoma of the head and neck that has spread to other parts of the body or has come back. Drugs used in chemotherapy, such as docetaxel, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy with or without erlotinib hydrochloride may be an effective treatment for squamous cell carcinoma of the head and neck.
详细描述
PRIMARY OBJECTIVES:
I. Assess the efficacy of adding erlotinib hydrochloride (erlotinib) to chemotherapy to improve progression free survival in patients with metastatic or recurrent squamous cell carcinoma of the head and neck.
SECONDARY OBJECTIVES:
I. Evaluate overall survival, response rate, disease control rate, and duration of response by treatment with or without erlotinib.
II. Evaluate quality of life (patient reported outcomes) by treatment with or without erlotinib.
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
- Double (Participant, Investigator)
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
- •Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, hypopharynx or larynx; metastatic or recurrent lesions of the nasopharynx and sinus are excluded
- •Radiologically measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; measurable lymph nodes are required to be >= 15 mm in size (short axis diameter)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- •Platelet count >= 100 x 10^9/L
- •Total bilirubin =< upper limit of normal (ULN) (excluding Gilbert's disease)
- •Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
- •Alkaline phosphatase =< 2.5 x ULN
- •Serum creatinine =< 1.5 x ULN
- •Patients with reproductive potential (e.g., females menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures for the duration of study drug therapy and for at least 30 days after completion of study drug therapy; female patients of childbearing potential must provide a negative pregnancy test (serum or urine) =< 14 days prior to treatment initiation
- •Written informed consent to participate in the study according to the investigational review board (IRB) or independent ethics committee (IEC)
排除标准
- •Histology other than squamous cell carcinoma
- •Primary sites other than oral cavity, oropharynx, hypopharynx, and larynx
- •Prior palliative chemotherapy for metastatic or recurrent disease
- •Prior biological therapy for metastatic or recurrent disease within 3 weeks prior to randomization
- •Patients with known, untreated brain metastases; patients with treated (irradiated or resected) brain metastases are eligible if treatment was completed more than 28 days prior to study entry and if clinical neurologic function is stable
- •Pre-existing peripheral neuropathy >= grade 2
- •History of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g., Crohn's disease, ulcerative colitis); patients requiring feeding tubes are permitted
- •Other active malignancies requiring chemotherapy treatment within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical or breast cancer or superficial, resected melanoma
- •Serious underlying medical condition which would impair the ability of the patient to receive protocol treatment, in the opinion of the treating physician
- •History of allergic reactions to compounds of similar chemical composition to the study drugs (docetaxel, cisplatin, carboplatin, erlotinib or their excipients), or other drugs formulated with polysorbate 80
- •Any concurrent anti-cancer therapy, excluding hormonal therapy for prostate or breast cancer
- •Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent
- •Women who are pregnant or breast-feeding and women or men not practicing effective birth control
研究组 & 干预措施
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Docetaxel (Drug)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Carboplatin (Drug)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Cisplatin (Drug)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Erlotinib Hydrochloride (Drug)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Pharmacological Study (Other)
Arm A (combination chemotherapy and erlotinib hydrochloride)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment.
干预措施: Quality-of-Life Assessment (Other)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Carboplatin (Drug)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Cisplatin (Drug)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Docetaxel (Drug)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Pharmacological Study (Other)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Placebo (Other)
Arm B (combination chemotherapy and placebo)
Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 5 years
Kaplan-Meier methods will be used to summarize PFS. In the primary analysis, differences in PFS in Arm A versus Arm B will be tested using a stratified log-rank test with a two-sided alpha of 0.10. Hazard ratios for PFS will be presented using point estimates and 95% confidence intervals.
次要结局
- Number of Participants With Tumor Response (Complete Response [CR] + Partial Response [PR])(5 years)
- Disease Control (CR + PR + Stable Disease [SD])(5 years)
- Rash Rates(5 years)
- Overall Survival (OS)(5 years)