Lung Cancer

EA5221 / ACHIEVE



Chemotherapy Combined with Immunotherapy vs Immunotherapy alone for Older Adults with Stage IIIB-IV Lung Cancer, The ACHIEVE Trial

STATUS: Active


This phase III trial compares the effect of adding chemotherapy to immunotherapy (pembrolizumab) versus immunotherapy alone in treating patients with stage IIIB-IV lung cancer. 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 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 and chemotherapy may help stabilize lung cancer.
  • STEP 1 REGISTRATION

  • Patient must be ≥ 70 years of age

  • Patient must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%

  • Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with recurrence is allowed

  • Patient must have a tumor that is negative for EGFR mutation/ALK translocations or other actionable first line mutations in which patients would receive first-line oral tyrosine kinase inhibitors

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2

  • Patient must agree not to father children while on study and for 6 months after the last dose of protocol treatment

  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

  • Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained within 14 days prior to Step 1 registration)

  • Platelets ≥ 75,000/mcL (obtained within 14 days prior to Step 1 registration)

  • Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)

  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to Step 1 registration)

  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)

  • Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with actual body weight or measured) (obtained within 14 days prior to Step 1 registration)

  • Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial

  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have undetectable HCV viral

  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

  • Patient must be English or Spanish speaking to be eligible for the QOL component of the study * NOTE: Sites cannot translate the associated QOL forms

  • Patient must not have symptomatic central nervous system disease (CNS) metastases. Patients with a clinical history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable for at least 14 days prior to Step 1 registration and off all steroids for at least 24 hours prior to Step 1 registration. Patients with asymptomatic CNS metastases are eligible

  • Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed, and they have fully recovered from treatment related adverse events prior to Step 1 registration

  • Patient must not have had any prior immunotherapy for metastatic disease. Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed greater than 6 months prior to Step 1 registration

  • Patient must not have a history of uncontrolled autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto’s thyroiditis, lupus, inflammatory bowel disease

  • Patient must not be on immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal and/or topical steroids are eligible

  • Investigator must declare their intended chemotherapy regimen should their patient be randomized to Arm B (doublet vs singlet)

  • STEP 2 RANDOMIZATION

  • Patient must have completed the baseline Geriatric Assessment (GA) after Step 1 registration and prior to Step 2 randomization

United States
IA
Ankeny
Mission Cancer and Blood - Ankeny
Contact: Site Public Contact

Cedar Rapids
Mercy Hospital
Contact: Site Public Contact

Oncology Associates at Mercy Medical Center
Contact: Site Public Contact

Clive
Medical Oncology and Hematology Associates-West Des Moines
Contact: Site Public Contact

Mercy Cancer Center-West Lakes
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Des Moines
Medical Oncology and Hematology Associates-Des Moines
Contact: Site Public Contact

Mercy Medical Center - Des Moines
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Mission Cancer and Blood - Laurel
Contact: Site Public Contact

ID
Coeur D'Alene
Kootenai Health - Coeur d'Alene
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Post Falls
Kootenai Clinic Cancer Services - Post Falls
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Sandpoint
Kootenai Cancer Clinic
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

IL
Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Effingham
Carle Physician Group-Effingham
Contact: Site Public Contact
Email: Research@carle.com

Crossroads Cancer Center
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com

Springfield
Memorial Medical Center
Contact: Site Public Contact
Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
Contact: Site Public Contact

Springfield Clinic
Contact: Site Public Contact

Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com

MD
Baltimore
Sinai Hospital of Baltimore
Contact: Site Public Contact
Email: pridgely@lifebridgehealth.org

Westminster
William E Kahlert Regional Cancer Center/Sinai Hospital
Contact: Site Public Contact

MI
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Canton
Trinity Health IHA Medical Group Hematology Oncology - Canton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Flint
Genesee Cancer and Blood Disease Treatment Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesee Hematology Oncology PC
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesys Hurley Cancer Institute
Contact: Site Public Contact
Email: wstrong@ghci.org

Hurley Medical Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Lansing
University of Michigan Health - Sparrow Lansing
Contact: Site Public Contact
Email: harsha.trivedi@umhsparrow.org

Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Pontiac
21st Century Oncology-Pontiac
Contact: Site Public Contact
Email: Emily.Crofts@trinity-health.org

Saint Joseph Mercy Oakland
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

MO
Cape Girardeau
Saint Francis Medical Center
Contact: Site Public Contact
Email: sfmc@sfmc.net

MT
Anaconda
Community Hospital of Anaconda
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Bozeman
Bozeman Deaconess Hospital
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Great Falls
Benefis Healthcare- Sletten Cancer Institute
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Missoula
Community Medical Hospital
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

NY
Bronx
Montefiore Medical Center - Moses Campus
Contact: Site Public Contact
Email: eskwak@montefiore.org

Montefiore Medical Center-Einstein Campus
Contact: Site Public Contact
Email: eskwak@montefiore.org

OH
Belpre
Strecker Cancer Center-Belpre
Contact: Site Public Contact
Email: sheree@columbusccop.org

Centerville
Miami Valley Hospital South
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Cleveland
MetroHealth Medical Center
Contact: Site Public Contact
Email: ababal@metrohealth.org

Columbus
The Mark H Zangmeister Center
Contact: Site Public Contact
Email: sheree@columbusccop.org

Dayton
Dayton Blood and Cancer Center
Contact: Site Public Contact

Miami Valley Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital North
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Franklin
Atrium Medical Center-Middletown Regional Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Greenville
Miami Valley Cancer Care and Infusion
Contact: Site Public Contact

Grove City
Mount Carmel Grove City Hospital
Contact: Site Public Contact
Email: sheree@columbusccop.org

Marysville
Memorial Hospital
Contact: Site Public Contact
Email: sheree@columbusccop.org

Mount Vernon
Knox Community Hospital
Contact: Site Public Contact
Email: sheree@columbusccop.org

Newark
Licking Memorial Hospital
Contact: Site Public Contact
Email: sheree@columbusccop.org

Springfield
Springfield Regional Cancer Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Troy
Upper Valley Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Zanesville
Genesis Healthcare System Cancer Care Center
Contact: Site Public Contact
Email: sheree@columbusccop.org

PA
Bryn Mawr
Bryn Mawr Hospital
Contact: Site Public Contact
Email: turzoe@mlhs.org

Media
Riddle Memorial Hospital
Contact: Site Public Contact
Email: turzoe@mlhs.org

Paoli
Paoli Memorial Hospital
Contact: Site Public Contact
Email: turzoe@mlhs.org

Philadelphia
ECOG-ACRIN Cancer Research Group
Contact: Megan Ann Baumgart
Email: megan_baumgart@urmc.rochester.edu

West Reading
Reading Hospital
Contact: Site Public Contact

Wynnewood
Lankenau Medical Center
Contact: Site Public Contact
Email: turzoe@mlhs.org

WI
Appleton
ThedaCare Regional Cancer Center
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Berlin
ThedaCare Cancer Care - Berlin
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

La Crosse
Gundersen Lutheran Medical Center
Contact: Site Public Contact
Email: cancerctr@gundersenhealth.org

Mukwonago
ProHealth D N Greenwald Center
Contact: Site Public Contact
Email: research.institute@phci.org

Neenah
ThedaCare Regional Medical Center - Neenah
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

New London
ThedaCare Cancer Care - New London
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Contact: Site Public Contact

Oshkosh
ThedaCare Cancer Care - Oshkosh
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Shawano
ThedaCare Cancer Care - Shawano
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Waukesha
ProHealth Waukesha Memorial Hospital
Contact: Site Public Contact

UW Cancer Center at ProHealth Care
Contact: Site Public Contact
Email: Chanda.miller@phci.org

Waupaca
ThedaCare Cancer Care - Waupaca
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

PRIMARY OBJECTIVE:
I. To evaluate whether there is an improvement in overall survival (OS) with chemotherapy combined with pembrolizumab compared to single agent pembrolizumab in this vulnerable older adult patient population.

SECONDARY OBJECTIVES:
I. To evaluate any difference in progression free survival (PFS) with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab.
II. To evaluate the difference in PFS rate at 3 months and at 6 months with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab.
III. To evaluate the difference in best objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria to assess whether chemotherapy combined with pembrolizumab results in improved response rates compared to treatment with single agent pembrolizumab.
IV. To evaluate toxicity in those treated with chemotherapy combined with pembrolizumab compared to those treated with single agent pembrolizumab.
V. To evaluate patient reported quality of life (QOL) evaluations between treatment arms.

EXPLORATORY OBJECTIVES:
I. To compare safety and tolerability between treatment arms including but not limited to number of additional lab draws, scan appointments, infusion visits, falls, emergency department visits, and hospitalization related to treatment toxicity.
II. To explore factors within the pre-treatment geriatric assessment (GA) as predictors of toxicity and outcomes. To describe changes between the intended chemotherapy treatment planned versus treatment given and referrals placed by treating provider based on GA results.
III. To evaluate the assessment of a novel, composite fPFS score using disease progression/functional impairment assessment as a potential correlate to OS in this vulnerable population.
IV. To evaluate the correlation of 3-months PFS with OS as a potential surrogate of OS benefit.
V. To evaluate the correlation of 6-months PFS with OS as a potential surrogate of OS benefit.
VI. To assess elective dose intensity of chemotherapy of patients who receive doublet chemotherapy versus single agent chemotherapy.

EXPLORATORY CORRELATIVE OBJECTIVE:
I. To relate gut microbe abundances to treatment outcomes, toxicity, and geriatric assessments.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

INDUCTION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive investigator's choice of a chemotherapy regimen: 1) Pemetrexed IV over 10 minutes + carboplatin IV over 30-60 minutes on day 1 of each cycle; 2) Nab-paclitaxel IV over 30 on days 1, 8, and 15 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 3) Paclitaxel IV over 1 hour on day 1, 8, and 15 of each cycle or over 3 hours on day 1 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 4) Nab-paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle; 5) Paclitaxel IV over 3 hours on day 1 of each cycle or over 1 hour on days 1, 8, and 15 of each cycle; or 6) Pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity.

All patients undergo magnetic resonance imaging (MRI) at baseline and computed tomography (CT) and/or positron emission tomography (PET) on the trial at baseline and throughout the trial. Patients may also undergo stool sample collection at baseline and on the trial. 

After completion of study treatment, patients are followed up every 3 months if < 2 years from randomization and every 6 months if 2-5 years from Step 1 registration.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.


EA5221 / ACHIEVE Home Page
ECOG-ACRIN Cancer Research Group