Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 8,300
- 试验地点
- 3,186
- 主要终点
- Central and local clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105
研究概览
简要总结
This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes.
详细描述
PRIMARY OBJECTIVES:
I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies.
II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
SECONDARY OBJECTIVES:
I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent development of targeted therapies against genotype-defined subpopulations in the adjuvant and recurrent settings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 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
- •PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
- •For pre-surgical patients
- •Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology; patients with squamous cell carcinoma are eligible
- •Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
- •For post-surgical patients
- •Completely resected non-small cell lung cancer with negative margins (R0); patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
- •Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Age ≥ 18 years
- •No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
- •No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
- •No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
- •No patients known to be pregnant or lactating
- •Patients who have had local genotyping are eligible, regardless of the local result
- •No patients with recurrence of lung cancer after prior resection
- •Note: Post-surgical patients should proceed to registration immediately following preregistration
- •PATIENT REGISTRATION ELIGIBILITY CRITERIA:
- •Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
- •Completely resected NSCLC with negative margins (R0); cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology
- •Pathologic stage IIIA, IIA or IIB, or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
- •Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
- •In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows:
- •Squamous patients:
- •No adjuvant therapy permitted, register patient within 77 days following surgery
- •Non-squamous patients:
- •If no adjuvant therapy, register patient within 75 days following surgery
- •If adjuvant chemotherapy or radiotherapy only, register patient within 225 days following surgery
- •If adjuvant chemotherapy and radiation, register patient within 285 days following surgery
排除标准
- 未提供
研究组 & 干预措施
A081105 Arm B (placebo)
Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Placebo Administration (Other)
A081105 Arm B (placebo)
Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Cytology Specimen Collection Procedure (Other)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Positron Emission Tomography (Procedure)
A081105 Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
干预措施: Clinical Observation (Other)
E4512 Arm A (crizotinib)
Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Cytology Specimen Collection Procedure (Other)
A081105 Arm A (blinded erlotinib hydrochloride)
Blinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Cytology Specimen Collection Procedure (Other)
A081105 Arm C (unblinded erlotinib hydrochloride)
Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Cytology Specimen Collection Procedure (Other)
E4512 Arm B (observation)
Patients undergo observation.
干预措施: Cytology Specimen Collection Procedure (Other)
E4512 Arm B (observation)
Patients undergo observation.
干预措施: Clinical Observation (Other)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Computed Tomography (Procedure)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Clinical Observation (Other)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Pemetrexed Disodium (Drug)
A081105 Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
干预措施: Cytology Specimen Collection Procedure (Other)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Paclitaxel (Drug)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Computed Tomography (Procedure)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Cytology Specimen Collection Procedure (Other)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Echocardiography Test (Procedure)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Biospecimen Collection (Procedure)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Clinical Observation (Other)
E4512 Arm A (crizotinib)
Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Crizotinib (Drug)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine Hydrochloride (Drug)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pemetrexed (Drug)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Nivolumab (Biological)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Gemcitabine Hydrochloride (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pemetrexed Disodium (Drug)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
A081105 Arm C (unblinded erlotinib hydrochloride)
Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Erlotinib (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pemetrexed (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine Hydrochloride (Drug)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Carboplatin (Drug)
A081801 Arm B (platinum doublet, sequential pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Cisplatin (Drug)
A081801 Arm A (platinum doublet, observation)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
干预措施: Pemetrexed (Drug)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Positron Emission Tomography (Procedure)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Echocardiography Test (Procedure)
EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.
干预措施: Biospecimen Collection (Procedure)
EA5142 Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
干预措施: Cytology Specimen Collection Procedure (Other)
A081801 Arm C (platinum doublet, combination pembrolizumab)
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pemetrexed Disodium (Drug)
结局指标
主要结局
Central and local clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105
时间窗: Up to 4 years
Central and local clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, will be measured by the rate of accrual.
Feasibility of research grade formalin-fixed, paraffin-embedded tissue collection for Center for Cancer Genomics (CCG) analysis
时间窗: Up to 4 years
Research grade formalin-fixed, paraffin-embedded tissue collection for Center for CCG analysis, will be measured by adequate specimens collected per month.
Central and local clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105
时间窗: Up to 4 years
Central and local clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, will be measured by the rate of accrual.
Feasibility of research grade formalin-fixed, paraffin-embedded tissue collection for Center for Cancer Genomics (CCG) analysis
时间窗: Up to 4 years
Research grade formalin-fixed, paraffin-embedded tissue collection for Center for CCG analysis, will be measured by adequate specimens collected per month.
次要结局
- Disease free survival (DFS) rate for lung cancers which are wild-type for EGFR and ALK(Time from resection to the earliest of documented disease recurrence confirmed by biopsy, development of a new lung cancer confirmed by biopsy, or death from any cause, assessed at 2 years)
- Agreement of local genotyping methods (direct sequencing of EGFR, ALK fluorescence in situ hybridization [FISH]) with central Clinical Laboratory Improvement Amendments genotyping(Up to 5 years)
- Disease free survival (DFS) rate for lung cancers which are wild-type for EGFR and ALK(Time from resection to the earliest of documented disease recurrence confirmed by biopsy, development of a new lung cancer confirmed by biopsy, or death from any cause, assessed at 2 years)
- Agreement of local genotyping methods (direct sequencing of EGFR, ALK fluorescence in situ hybridization [FISH]) with central Clinical Laboratory Improvement Amendments genotyping(Up to 5 years)