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Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, ALCHEMIST Chemo-IO Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04267848
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : July 2, 2020
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase III ALCHEMIST trial compares the addition of pembrolizumab to usual chemotherapy versus usual chemotherapy for the treatment of stage IB, II, or IIIA non-small cell lung cancer that has been removed by surgery. 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. Drugs used in chemotherapy, such as cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel, 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. The purpose of this trial is to find out if the addition of pembrolizumab to usual chemotherapy is better or worse than usual chemotherapy alone for non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Lung Non-Small Cell Carcinoma Stage IB Lung Cancer AJCC v7 Stage II Lung Cancer AJCC v7 Stage IIA Lung Cancer AJCC v7 Stage IIB Lung Cancer AJCC v7 Stage IIIA Lung Cancer AJCC v7 Drug: Carboplatin Drug: Cisplatin Drug: Gemcitabine Hydrochloride Other: Observation Drug: Paclitaxel Biological: Pembrolizumab Drug: Pemetrexed Disodium Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1263 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Integration of Immunotherapy Into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO
Actual Study Start Date : June 3, 2020
Estimated Primary Completion Date : December 15, 2024
Estimated Study Completion Date : December 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • FF 10832
  • FF-10832
  • FF10832
  • Gemcitabine HCI
  • Gemzar
  • LY-188011
  • LY188011

Other: Observation
Undergo observation
Other Names:
  • Inspection
  • Visual Inspection

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Experimental: 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 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 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Experimental: 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 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 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Disease free survival (DFS) [ Time Frame: From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion ]
    Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. DFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.

  2. Overall survival (OS) [ Time Frame: From randomization to death from any cause, assessed up to 8 years after accrual completion ]
    Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.


Secondary Outcome Measures :
  1. DFS between combination pembrolizumab with standard of care vs. sequential pembrolizumab [ Time Frame: From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion ]
  2. OS between combination pembrolizumab with standard of care vs. sequential pembrolizumab [ Time Frame: From randomization to death from any cause, assessed up to 8 years after accrual completion ]
  3. Incidence of adverse events [ Time Frame: Up to 10 years ]
    The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The frequency and percentage of grade 3+ adverse events will be compared between the 2 experimental treatment arms and the control as well as between the two experimental arms. We will also compare the rate of drug discontinuation due to adverse events between the experimental treatment arms and control, and between the two experimental arms. Comparisons between arms will be made by using the Chi-square test. Analysis of the overall adverse event rates, as well as specific events of interest will involve Chi-square tests or Fisher's exact tests.

  4. DFS between each experimental pembrolizumab plus standard of care arms vs. standard of care by PD-L1 expression status [ Time Frame: From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years after accrual completion ]
    Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models.

  5. OS between each experimental pembrolizumab plus standard of care arms vs. standard of care by PD-L1 expression status [ Time Frame: From randomization to death from any cause, assessed up to 8 years after accrual completion ]
    Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be used as the primary analytical method, where all baseline covariates will be considered in the univariable models and subsequently in the multivariable models based on the criteria for selection for the multivariable models.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously registered to A151216
  • Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation
  • Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative)
  • Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, or SP263

    • Note: Local testing results of EGFR and ALK by a local Clinical Laboratory Improvement Act (CLIA) certified laboratory is acceptable. The report must indicate the result as well as the CLIA number of the laboratory that performed the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, or SP263 are acceptable for enrollment on A081801. Patients with local results for EGFR, ALK and PD-L1 still need to be registered to A151216 and follow all the submissions requirements but do NOT need to wait for the results to proceed to A081801 registration
  • Completely resected stage IB (>= 4 cm), II or IIIA non-small cell lung cancer (NSCLC) with negative margins (complete R0 resection). Patients will be staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2010

    • Note: Patients with pathologic N2 disease, completely resected, are eligible. However, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population
  • Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery
  • No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
  • No prior allogeneic tissue/solid organ transplant
  • Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
  • No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
  • No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
  • No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that have undergone potentially curative therapy are eligible
  • No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 8 gm/dl
  • Calculated (Calc.) creatinine clearance >= 45 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04267848


Locations
Show Show 428 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jacob M Sands Alliance for Clinical Trials in Oncology
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04267848    
Other Study ID Numbers: NCI-2020-00751
NCI-2020-00751 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
A081801 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A081801 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: July 2, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Paclitaxel
Cisplatin
Carboplatin
Pembrolizumab
Albumin-Bound Paclitaxel
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors