Integration of Immunotherapy Into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO (ACCIO)

  • STATUS
    Recruiting
  • End date
    Dec 15, 2024
  • participants needed
    1210
  • sponsor
    National Cancer Institute (NCI)
Updated on 20 September 2022
Investigator
Donald F. Busiek
Primary Contact
Cancer Care and Hematology-Fort Collins (8.1 mi away) Contact
+466 other location
platelet count
paclitaxel
carcinoma
pemetrexed
neutrophil count
carboplatin
gemcitabine
pembrolizumab

Summary

This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for the treatment of stage IIA, IIB IIIA or IIIB 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. Chemotherapy drugs, 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. Giving pembrolizumab with usual chemotherapy may help increase survival times in patients with stage IIA, IIB IIIA or IIIB non-small cell lung cancer.

Description

PRIMARY OBJECTIVE:

I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) between the two treatment arms in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

II. To compare the adverse event rates and drug discontinuation rates due to adverse events in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

III. To compare the adverse event (AE) rates for Arms B and C with A (prior to Update #7) and estimate the DFS and OS in Arm A.

IV. To compare the DFS and OS in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer that receive at least 2 cycles of initial adjuvant chemotherapy.

QUALITY OF LIFE OBJECTIVES:

I. To compare patient-reported quality of life (QOL) one year after randomization as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core (C)30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B), and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C).

II. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC QLQ-C30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B) and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C).

III. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as assessed by the EORTC QLQ-Lung Cancer (LC13).

CORRELATIVE SCIENCE OBJECTIVES:

I. To compare the DFS and OS in the PD-L1 subgroup of patients with PD-L1 expression status (>= 1% vs < 1%).

II. To compare the DFS and OS by tumor mutational burden status (high vs. low) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (CLOSED AS OF UPDATE #7):

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 or every 6 weeks for 16 cycles (patients enrolled after 10/14/2020) 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 or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) 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 treatment, patients are followed up at 6 weeks, then every 3 months for 2 years from randomization, every 6 months for years 2-4, and then annually for up to 10 years from randomization.

Details
Condition Lung Non-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIA Lung Cancer AJCC v8, Stage IIB Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8
Treatment questionnaire administration, cisplatin, gemcitabine hydrochloride, quality-of-life assessment, carboplatin, Paclitaxel, Pembrolizumab, Observation, pemetrexed disodium
Clinical Study IdentifierNCT04267848
SponsorNational Cancer Institute (NCI)
Last Modified on20 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Previously registered to A151216 (NCT02194738)
Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only)
Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only)
Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N 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, EIL3N 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 IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer
(NSCLC) (squamous or non-squamous) with negative margins (complete R0
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
resection). Patients will be staged according to the 8th edition of the
American Joint Committee on Cancer (AJCC) Staging Manual, 2017
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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
Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
No prior allogeneic tissue/solid organ transplant
No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
Age >= 18 years
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
Absolute neutrophil count (ANC) >= 1,500/mm^3
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
Platelet count >= 100,000/mm^3
Hemoglobin >= 8 gm/dl
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
Calculated (Calc.) creatinine clearance >= 45 mL/min
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
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Exclusion Criteria

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
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