A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult With Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 304
- 试验地点
- 612
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase III trial compares the effect of adding chemotherapy to immunotherapy (pembrolizumab) versus immunotherapy alone in treating patients with stage IIIB-IV lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs 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. Giving pembrolizumab and chemotherapy may help stabilize lung cancer.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate whether there is an improvement in overall survival (OS) with chemotherapy combined with pembrolizumab compared to single agent pembrolizumab in this vulnerable older adult patient population.
SECONDARY OBJECTIVES:
I. To evaluate any difference in progression free survival (PFS) with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab.
II. To evaluate the difference in PFS rate at 3 months and at 6 months with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab.
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •STEP 1 REGISTRATION
- •Patient must be ≥ 70 years of age
- •Patient must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%
- •Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with recurrence is allowed
- •Patient must have a tumor that is negative for EGFR mutation/ALK translocations or other actionable first line mutations in which patients would receive first-line oral tyrosine kinase inhibitors
- •Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
- •Patient must agree not to father children while on study and for 6 months after the last dose of protocol treatment
- •Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
- •Absolute neutrophil count (ANC) ≥ 1,500/uL (obtained within 14 days prior to Step 1 registration)
- •Platelets ≥ 75,000/uL (obtained within 14 days prior to Step 1 registration)
- •Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to Step 1 registration)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)
- •Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with actual body weight or measured) (obtained within 14 days prior to Step 1 registration)
- •Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have undetectable HCV viral
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Patient must be English or Spanish speaking to be eligible for the QOL component of the study
- •NOTE: Sites cannot translate the associated GA or QOL forms
- •Patient must not have symptomatic central nervous system disease (CNS) metastases. Patients with a clinical history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable for at least 14 days prior to Step 1 registration and off all steroids for at least 24 hours prior to Step 1 registration. Patients with asymptomatic CNS metastases are eligible
- •Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed, and they have fully recovered from treatment related adverse events prior to Step 1 registration
- •Patient must not have had any prior immunotherapy for metastatic disease. Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed greater than 6 months prior to Step 1 registration
- •Patient must not have a history of uncontrolled autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto's thyroiditis, lupus, inflammatory bowel disease
- •Patient must not be on immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal and/or topical steroids are eligible
- •Patient must have baseline imaging done assessing all measurable or non-measurable sites of disease within 45 days prior to Step 1 registration
- •Investigator must declare their intended chemotherapy regimen should their patient be randomized to Arm B (doublet versus[vs] singlet)
- •STEP 2 RANDOMIZATION
- •Patient must have completed the baseline Geriatric Assessment (GA) after Step 1 registration and prior to Step 2 randomization
排除标准
- 未提供
研究组 & 干预措施
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Computed Tomography (Procedure)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Arm A (pembrolizumab)
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial.
干预措施: Computed Tomography (Procedure)
Arm A (pembrolizumab)
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Positron Emission Tomography (Procedure)
Arm A (pembrolizumab)
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm A (pembrolizumab)
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Carboplatin (Drug)
Arm A (pembrolizumab)
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial.
干预措施: Pembrolizumab (Biological)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Pembrolizumab (Biological)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Pemetrexed (Drug)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Nab-paclitaxel (Drug)
Arm B (pembrolizumab, chemotherapy)
See Detailed Description
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: From randomization to death from any cause, and patients who are alive at the time of final analysis will be censored at the last date of contact, assessed up to 5 years
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate hazard ratios. Comparison of OS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 0.025. Other comparisons of groups will be made using the log rank test and Cox modeling.
次要结局
- Progression free survival (PFS)(From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
- Six month PFS(From randomization to documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first, assessed at 6 months)
- Best objective response(Up to 5 years)
- Incidence of adverse events(Up to 2 years)
- Evaluation of quality of life (QOL) measures(Baseline up to 6 months)