A Phase II Study of the Effects of Pembrolizumab on Quality of Life for Patients With Treatment-Naïve, Advanced or Metastatic NSCLC and Poor Performance Status
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Change in EORTC QLQ-C30 Quality of Life score
研究概览
简要总结
This single center open-label trial will enroll a single cohort of patients with advanced non-small cell lung cancer (NSCLC) who are ineligible for treatment with curative intent due to 1) disease stage IV, or 2) inability to tolerate intensive surgery or chemo-radiation. Patients will be eligible for the trial if ISMMS reviewed samples from tumor biopsy have a PDL-1 TPS ≥ 1% and have ECOG performance status rated 2 or 3. All patients will receive anti PD-1 therapy with pembrolizumab 200mg IV every 3 weeks, during which patients will also undergo serial QOL assessments.
This trial will follow a phase II single arm, open label design. The study will enroll 45 patients evaluable for the primary endpoint of which will be change in QOL as measured by the EORTC's QLQ-C30 between Day 1 and Day 84 +/- 7 days. Secondary outcomes including evaluation for development of confounding mental health conditions will be evaluated via serial HADS assessments. Concomitant radiographic assessment with PET/CT, regardless of the doses of pembrolizumab received, will allow for evaluation of secondary efficacy outcomes, including disease response by RECIST 1.1 criteria.
详细描述
Primary Objective To assess the effects of first-line pembrolizumab upon patient quality of life in patients with metastatic non-small cell lung cancer who are ineligible for standard first line treatments due to poor performance status (ECOG PS of 2 or 3).
Secondary Objectives
- To assess the clinical outcomes of first-line pembrolizumab in this patient population.
- To evaluate the toxicity of first-line pembrolizumab in this patient population.
- To assess patient reported QOL in the emotional domain (using HADS).
- To assess baseline patient-reported performance status and correlate with QOL and clinical outcomes.
- To assess baseline geriatric assessment score for patients 70 years of age and older and correlate with QOL and clinical outcomes.
- To correlate QOL and outcomes with demographic and clinical factors including: age, gender, race/ethnicity, zip code, insurance type, presence/absence of CNS metastases, PD-L1 TPS (<1%, 1-49%, ≥50%), geriatric assessment scores, presence or absence of other major organ dysfunction (e.g. CKD), ECOG 2 vs 3, adverse events: G2, G3-4.
Primary Endpoint Change in QOL score after 12 weeks of treatment as measured by EORTC's QLQ-C30
Secondary Endpoints
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Men and women, aged 18 years and older, with locally advanced NSCLC who are ineligible for definitive surgical resection or concurrent chemoradiation, or metastatic NSCLC
- •Patients must not have received any systemic therapy for metastatic cancer
- •Patients must not have received any PD-1 or PD-L1 inhibitor
- •ECOG performance status of 2 or 3 at the time of consent and on the first day of therapy
- •Patients may not have a molecular alteration in ALK, ROS1, EGFR, BRAF, NTRK, RET, MET, or any other gene for which first-line FDA approved targeted therapy exists.
- •Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
- •Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS directed therapy is not required and is unlikely to be required during the first cycle of therapy.
- •Patients with HIV on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this trial.
- •Adequate organ and marrow function as defined below:
- •Leukocytes ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,000/mcL
- •Platelets ≥ 100,000/mcl
- •Total bilirubin ≤ 1.5 x ULN
- •AST (SGOT)/ALT (SPGT) ≤ 3 x ULN or ≤5 x ULN if liver metastases present
- •GFR (Cockroft-Gault) ≥ 30 mL/min
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 3 days prior to C1D1 of pembrolizumab therapy. For the purposes of this trial, WOCBP are defined as women who have had a menstrual period within the last 48 months.
- •Provision of signed and dated informed consent form
- •Ability to take the study medication, and complete the study questionnaires
- •Stated willingness to comply with all study procedures for the duration of the study
- •For women of reproductive potential, agreement to use highly effective contraception during study treatment and for at least 4 months after the final dose
- •For men of reproductive potential, agreement to use condoms or other methods to ensure effective contraception with female partners of reproductive potential
排除标准
- •Autoimmune conditions requiring >10mg prednisone (or its equivalent) of daily therapy or other systemic immunosuppressive therapy.
- •Patients who are receiving other investigational agents
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients with known leptomeningeal disease for which CNS therapy is required
- •Pregnant or lactating patients
研究组 & 干预措施
Pembrolizumab
Patients will be treated with the standard dose of pembrolizumab (200mg IV every 3 weeks) for the first 12 weeks of the study. After week 12 assessments, patients without objective progression of disease are eligible to transition to Q6W dosing of pembrolizumab 400mg IV.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Change in EORTC QLQ-C30 Quality of Life score
时间窗: Baseline and 12 weeks post-treatment
Change in quality of life (QOL) score at 12 weeks post-treatment compared to baseline with pembrolizumab as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The scale ranges from 1=very poor to 7 = excellent. The higher the score the better the quality of life.
次要结局
- Number of Emergency Room Visits(at 12 weeks post-treatment)
- Change in EORTC QLQ-C30 Quality of Life score(Baseline and 6 weeks post-treatment)
- Change in EORTC's QLQ-LC13 Quality of Life (QOL) score(Baseline and 12 weeks post-treatment)
- Change in Hospital Anxiety and Depression Scale (HADS) Quality of Life (QOL) score(Baseline and 12 weeks post-treatment)
- Overall Survival (OS)(at 12 weeks post-treatment)
- Patient Reported Eastern Cooperative Oncology Group (ECOG) performance status(at 12 weeks post-treatment)
- Objective Response Rate(at 12 weeks post-treatment)
- Progression-Free Survival (PFS)(at 12 weeks post-treatment)
- Number of Hospitalizations(at 12 weeks post-treatment)
- Number of Adverse Events(at 12 weeks post-treatment)
- Physician reported ECOG Performance Status Scale(at 12 weeks post-treatment)
- Cancer Aging and Research Group (CARG) Chemo-Toxicity Calculator Survey Score(Baseline)
- Patient Reported Outcome (PRO) completion rate(at 12 weeks post-treatment)
研究者
Deborah Doroshow
Assistant Professor of Medicine
Icahn School of Medicine at Mount Sinai