Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

  • STATUS
    Recruiting
  • participants needed
    8300
  • sponsor
    National Cancer Institute (NCI)
Updated on 26 November 2020
Investigator
Marvin J. Feldman
Primary Contact
Northwest Hospital Center (3.8 mi away) Contact
+1097 other location
paclitaxel
cancer
carcinoma
squamous cell carcinoma
lung cancer
metastasis
pemetrexed
carboplatin
erlotinib
tumor cells
gemcitabine
pembrolizumab
nivolumab
adenocarcinoma
adjuvant chemotherapy
crizotinib

Summary

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.

Description

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.

II. To cross-validate local genotyping assays for epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard.

EXPLORATORY/OTHER OBJECTIVES:

I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.

II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for potentially eligible patients.

III. To study the clinical significance of circulating tumor DNA within the plasma cell-free DNA (cfDNA) from early stage lung cancer patients.

OUTLINE

STEP 1 (SCREENING): Patients undergo collection of blood and tissue samples for EGFR, ALK, and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.

STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 4 treatment subprotocols.

A081105: Patients are randomized to 1 of 4 treatment arms.

ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM B (PLACEBO- CLOSED 06/14/17): 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.

ARM C (UNBLINDED ERLOTINIB): 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.

ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.

E4512: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive crizotinib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation.

EA5142: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

ARM II: Patients are followed serially with imaging for 1 year.

A081801: Patients are randomized to 1 of 3 arms.

ARM A:

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.

ARM B:

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 intravenously (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.

ARM C:

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.

*ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle.

DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle.

DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.

DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 of each cycle.

After completion of study, patients that are not enrolled on either A081105, E4512, EA5142, or A081801 are followed up every 6 months for 5 years.

Details
Treatment clinical observation, laboratory biomarker analysis, cisplatin, gemcitabine hydrochloride, carboplatin, cytology specimen collection procedure, erlotinib hydrochloride, Placebo, Gemcitabine, Paclitaxel, Pembrolizumab, Pemetrexed, Nivolumab, Erlotinib, pemetrexed disodium, Placebo Administration, Crizotinib
Clinical Study IdentifierNCT02194738
SponsorNational Cancer Institute (NCI)
Last Modified on26 November 2020

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Stage II Non-Small Cell Lung Cancer AJCC v7 or Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 or Stage IIB Lung Squamous Cell Carcinoma AJCC v7 or St...?
Do you have any of these conditions: Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 or Lung Adenocarcinoma or Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 or Stage IIIA Lung Squamous ...?
Do you have any of these conditions: Resectable Lung Non-Small Cell Carcinoma or Stage IIIA Lung Non-Small Cell Cancer AJCC v7 or Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 or Stage ...?
Do you have any of these conditions: Stage II Lung Non-Small Cell Cancer AJCC v7 or Lung Large Cell Carcinoma or Stage IB Lung Squamous Cell Carcinoma AJCC v7 or Stage IIIA Lung Squamous ...?
Do you have any of these conditions: Stage IB Squamous Cell Lung Carcinoma AJCC v7 or Stage II Squamous Cell Lung Carcinoma AJCC v7 or Lung Large Cell Carcinoma or Stage IIIA Squamous Cel...?
Do you have any of these conditions: Large Cell Lung Carcinoma or Stage IIA Lung Squamous Cell Carcinoma AJCC v7 or Lung Adenocarcinoma or Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 ...?
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
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
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