Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- 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

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Screening
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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)
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
Placebo Comparator
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)
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
  • Other: Placebo Administration
    Given PO
Experimental
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.
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
  • Drug: Erlotinib
    Given PO
  • Drug: Erlotinib Hydrochloride
    Given PO
    Other names:
    • Cp-358,774
    • OSI-774
    • Tarceva
Active Comparator
A081105 Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
  • Other: Clinical Observation
    Undergo observation
    Other names:
    • observation
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
Active Comparator
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.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Other: Clinical Observation
    Undergo observation
    Other names:
    • observation
  • Drug: Gemcitabine
    Given IV
    Other names:
    • dFdC
    • dFdCyd
    • Difluorodeoxycytidine
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • FF 10832
    • FF-10832
    • FF10832
    • Gemcitabine HCI
    • Gemzar
    • LY-188011
    • LY188011
  • Drug: Paclitaxel
    Given IV
    Other names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate
  • Drug: Pemetrexed Disodium
    Given IV
    Other names:
    • Alimta
    • Almita
    • LY231514
    • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Experimental
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.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Drug: Gemcitabine
    Given IV
    Other names:
    • dFdC
    • dFdCyd
    • Difluorodeoxycytidine
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • FF 10832
    • FF-10832
    • FF10832
    • Gemcitabine HCI
    • Gemzar
    • LY-188011
    • LY188011
  • Drug: Paclitaxel
    Given IV
    Other names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate
  • Drug: Pemetrexed Disodium
    Given IV
    Other names:
    • Alimta
    • Almita
    • LY231514
    • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Experimental
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.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Cisplatin
    Given IV
    Other names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Drug: Gemcitabine
    Given IV
    Other names:
    • dFdC
    • dFdCyd
    • Difluorodeoxycytidine
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • FF 10832
    • FF-10832
    • FF10832
    • Gemcitabine HCI
    • Gemzar
    • LY-188011
    • LY188011
  • Drug: Paclitaxel
    Given IV
    Other names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Drug: Pemetrexed
    Given IV
    Other names:
    • MTA
    • Multitargeted Antifolate
  • Drug: Pemetrexed Disodium
    Given IV
    Other names:
    • Alimta
    • Almita
    • LY231514
    • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Experimental
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.
  • Drug: Crizotinib
    Given PO
    Other names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
Active Comparator
E4512 Arm B (observation)
Patients undergo observation.
  • Other: Clinical Observation
    Undergo observation
    Other names:
    • observation
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
Experimental
EA5142 Arm I (nivolumab)
Patients receive nivolumab 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.
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling
  • Biological: Nivolumab
    Given IV
    Other names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
Active Comparator
EA5142 Arm II (observation)
Patients are followed serially with imaging for 1 year.
  • Other: Cytology Specimen Collection Procedure
    Undergo collection of blood and tissue
    Other names:
    • Cytologic Sampling

Recruiting Locations

More Details

Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.