A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 125
- 试验地点
- 71
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to determine whether the combination of palbociclib with cetuximab is superior to cetuximab in prolonging overall survival in HPV-negative, cetuximab-naive patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
- •Measurable disease as defined per RECIST v. 1.
- •Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measureable if disease progression at the treated site after completion of therapy is clearly documented.
- •HPV- negative SCCHN tumor as determined per institutional standard (eg, p16 IHC; multiplex nucleic acid sequence based amplification [NASBA] or other polymerase chain reaction [PCR]-based assays).
- •Documented progressive disease according to RECIST v1.1 (Appendix 2) following receipt of at least 2 cycles of one platinum-containing chemotherapy regimen administered for R/M disease (min. 50 mg/m2 for cisplatin, minimum area under the curve [AUC] > 4 for carboplatin).
- •Availability of a tumor tissue specimen (ie, archived formalin fixed paraffin embedded tissue [block preferred, or 15 unstained slides]), which will be used for centralized, retrospective biomarker analysis. If archived tumor tissue is not available, then a de novo biopsy will be required for patient participation.
排除标准
- •Prior nasopharyngeal cancer, salivary gland or sinus tumors.
- •More than one chemotherapeutic regimen given for R/M disease. Prior treatment with immunotherapy is allowed.
- •Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
- •Progressive disease within 3 months after completion of curatively intended treatment for locoregionally advanced SCCHN.
- •Difficulty swallowing capsules.
- •Prior use of cetuximab in the R/M disease treatment setting (except cetuximab during curative radiotherapy)
研究组 & 干预措施
Palbociclib plus Cetuximab
Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.
干预措施: palbociclib (Drug)
Palbociclib plus Cetuximab
Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.
干预措施: Cetuximab (Drug)
Placebo plus Cetuximab
Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.
干预措施: Cetuximab (Drug)
Placebo plus Cetuximab
Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Baseline up to primary completion date (PCD) (about 34 months)
OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - randomization date +1)/30.4. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization had their OS times be censored at randomization. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.
次要结局
- Percentage of Participants With Objective Response (OR)(Baseline up to PCD (about 34 months))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)(Baseline up to PCD (about 34 months))
- Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab(Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2)
- Number of Participants With Treatment-Emergent Adverse Events(TEAEs)(From the first dose through and including 28 calendar days after the last administration of the study treatment (up to 6.9 years))
- Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)(Screening)
- Percentage of Participants With Clinical Benefit Response (CBR)(Baseline up to PCD (about 34 months))
- Duration of Response (DR)(Baseline up to PCD (about 34 months))
- Number of Participants With Laboratory Abnormalities(From the Screening (Day -28) through and including 28 calendar days after the last administration of the study treatment (up to 7 years))
- Trough Plasma Concentration (Ctrough) and Within-participant Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib(Pre-dose of Day 15 in Cycle 1 and Cycle 2)
- Progression Free Survival (PFS)(Baseline up to PCD (about 34 months))
- Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)(Baseline up to PCD (about 34 months))
- Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%(Screening)