Last updated on September 2018

Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer


Brief description of study

This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid ?Master Protocol? (S1400). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes a ?non-match? sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of care also with the goal of approval.

Detailed Study Description

PRIMARY OBJECTIVES:

Screening component:

I. To establish a National Clinical Trials Network (NCTN) mechanism for genomically screening large but homogeneous cancer populations and subsequently assigning and accruing simultaneously to a multi-sub-study ?Master Protocol.? II. To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study.

Sub-study-specific Objectives:

Design #1: Phase II/III Design:

III. To evaluate if there is sufficient evidence to continue to the Phase III component of the sub-study by comparing investigator-assessed progression-free survival (IA-PFS) between investigational therapy versus standard therapy (SoC) in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung. (Phase II) IV. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III) V. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III)

Design #2: Phase II followed by Phase III (Sequential Phase II to Phase III):

VI. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial). (Phase II) VII. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III) VIII. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III)

SECONDARY OBJECTIVES:

Sub-study-specific Objectives:

Design #1: Phase II/III Design:

I. To compare response rates (confirmed and unconfirmed, complete and partial responses) among patients randomized to receive investigational therapy versus SoC. (Phase II) II. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase II) III. To evaluate the duration of response (DoR) among patients who achieve a complete response (CR) or a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) (1.1). (Phase II) III. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III) IV. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III)

Design #2: Phase II followed by Phase III (Sequential Phase II to Phase III):

V. To evaluate PFS and OS with investigational therapy. (Phase II) VI. To evaluate the DoR among patients who achieve a CR or PR (confirmed and unconfirmed) by RECIST 1.1. (Phase II) VII. To evaluate the frequency and severity of toxicities associated with investigational therapy. (Phase II) VIII. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III) IX. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III)

TERTIARY OBJECTIVES:

I. To evaluate the treatment arm randomization acceptance rate (TARAR) within each treatment arm of each sub-study defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. (Design #1: Phase II/III Design) II. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the targeted therapy (TT)/targeted therapy combination (TTC) beyond the chosen biomarker for biomarker-driven sub-studies.

III. To evaluate potentially predictive biomarkers for non-match therapy (NMT) in the non-match studies.

IV. To identify potential resistance biomarkers at disease progression. V. To establish a tissue/ blood repository from patients with refractory SCCA of the lung.

OUTLINE: Patients are assigned to a biomarker-driven targeted therapy phase II study. If the objectives response rate observed is judged sufficient, patients proceed to a randomized phase III trial and are randomized to biomarker-driven targeted therapy or standard of care.

S1400A: (CLOSED TO ACCRUAL 12/18/2015) Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are assigned to Arm I. Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period (Arm III).

ARM I: (CLOSED TO ACCRUAL 12/18/2015) Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 4/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #2 4/22/15)

ARM III: For patients assigned to Arm 1, MEDI4736: Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment with Arm 3, MEDI4736 for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period. Patients will only be able to restart treatment once; thus a maximum of two 12-month periods will be allowed. Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity.

S1400B (CLOSED TO ACCRUAL 12/12/2016): Patients with tumors positive for phosphoinositide 3-kinase (PI3KCA) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, GCD-0032 after disease progression on current treatment (Arm III).

ARM I: Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015)

ARM III: Re-Registration Treatment with GDC-0032 (Taselisib) Upon progression patients in Arm 2 may be eligible for Re-Registration to receive GDC-0032. Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400C (CLOSED TO ACCRUAL 09/01/2016): Patients with tumors positive for cyclin dependent kinase 4 (CDK4), cyclin D1 (CCND1), cyclin D2 (CCND2), and cyclin D3 (CCND3) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, palbociclib, after disease progression on current treatment (Arm III).

ARM I: Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015)

ARM III: Re-Registration Treatment with Palbociclib. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive palbociclib. Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

S1400D (CLOSED TO ACCRUAL 10/31/2016): Patients with tumors positive for fibroblast growth factor receptor (FGFR) 1, FGFR2, and FGFR3 are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, AZD4547, after disease progression on current treatment (Arm III).

ARM I: Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015)

ARM III: Re-Registration Treatment with AZD4547. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive AZD4547. Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400E (CLOSED TO ACCRUAL 11/25/2014): Patients with tumors positive for met proto-oncogene (MET) are randomized to 1 of 2 treatment arms. (permanently closed to accrual on 11/25/14)

ARM I: Patients receive rilotumumab IV on day 1 and erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400F: Patients with disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment receive durvalumab (IV over 60 minutes) and tremelimumab (IV over 60 minutes) on day 1 for courses 1-4 and durvalumab IV alone on day 1 of course 5 and subsequent courses until disease progression or unacceptable toxicity. Courses repeat every 28 days.

S1400G: Patients with tumors positive for homologous recombination repair deficiency receive talazoparib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1400I: Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up periodically for up to 3 years from date of screening registration.

Clinical Study Identifier: NCT02154490

Find a site near you

Start Over

Marshfield Clinic-Chippewa Center

Chippewa Falls, WI United States
  Connect »

Meharry Medical College

Nashville, TN United States
  Connect »

Margaret R Pardee Memorial Hospital

Hendersonville, NC United States
  Connect »

Mills-Peninsula Medical Center

Burlingame, CA United States
  Connect »

Decatur Memorial Hospital

Decatur, IL United States
  Connect »

University of Virginia Cancer Center

Charlottesville, VA United States
  Connect »

Cleveland Clinic Foundation

Cleveland, OH United States
  Connect »

Hardin Memorial Hospital

Elizabethtown, KY United States
  Connect »

Feather River Cancer Center

Paradise, CA United States
  Connect »

Sinai Hospital of Baltimore

Baltimore, MD United States
  Connect »

Sovah Health Martinsville

Martinsville, VA United States
  Connect »

Mary Imogene Bassett Hospital

Cooperstown, NY United States
  Connect »

Rapid City Regional Hospital

Rapid City, SD United States
  Connect »

Virginia Cancer Institute

Richmond, VA United States
  Connect »

Mercy Hospital

Coon Rapids, MN United States
  Connect »

University Pointe

West Chester, OH United States
  Connect »

Dekalb Medical Center

Decatur, GA United States
  Connect »

Northwest Hospital Center

Randallstown, MD United States
  Connect »

Kaiser Permanente-Oakland

Oakland, CA United States
  Connect »

Kootenai Cancer Center

Post Falls, ID United States
  Connect »

Fairbanks Memorial Hospital

Fairbanks, AK United States
  Connect »

Baptist Health Corbin

Corbin, KY United States
  Connect »

Baystate Medical Center

Springfield, MA United States
  Connect »

Saint Francis Cancer Center

Greenville, SC United States
  Connect »

PCR Oncology

Arroyo Grande, CA United States
  Connect »

MetroHealth Medical Center

Cleveland, OH United States
  Connect »

Saint Joseph Mercy Hospital

Ann Arbor, MI United States
  Connect »

Illinois CancerCare-Bloomington

Bloomington, IL United States
  Connect »

Kaiser Permanente-Lone Tree

Lone Tree, CO United States
  Connect »

Randolph Hospital

Asheboro, NC United States
  Connect »

Spartanburg Medical Center

Spartanburg, SC United States
  Connect »

Bryn Mawr Hospital

Bryn Mawr, PA United States
  Connect »

AMG Oncology - Naperville

Naperville, IL United States
  Connect »

Mercy Health Saint Mary's

Grand Rapids, MI United States
  Connect »

Vidant Oncology-Kinston

Kinston, NC United States
  Connect »

Olathe Medical Center

Olathe, KS United States
  Connect »

Northside Hospital

Atlanta, GA United States
  Connect »

Geauga Hospital

Chardon, OH United States
  Connect »

Assarian Cancer Center

Novi, MI United States
  Connect »

Lowell General Hospital

Lowell, MA United States
  Connect »

Ingalls Memorial Hospital

Harvey, IL United States
  Connect »

Adena Regional Medical Center

Chillicothe, OH United States
  Connect »

Carle Cancer Center

Urbana, IL United States
  Connect »

Katmai Oncology Group

Anchorage, AK United States
  Connect »

Mercy Hospital Joplin

Joplin, MO United States
  Connect »

Reid Health

Richmond, IN United States
  Connect »

Northwest Cancer Clinic

Kennewick, WA United States
  Connect »

Medical Center of Baton Rouge

Baton Rouge, LA United States
  Connect »

Ochsner Medical Center Jefferson

New Orleans, LA United States
  Connect »

Saint Francis Medical Center

Cape Girardeau, MO United States
  Connect »

Anchorage Oncology Centre

Anchorage, AK United States
  Connect »

Kaiser Permanente-Anaheim

Anaheim, CA United States
  Connect »

Kaiser Permanente-Baldwin Park

Baldwin Park, CA United States
  Connect »

Kaiser Permanente-Bellflower

Bellflower, CA United States
  Connect »

Kaiser Permanente - Harbor City

Harbor City, CA United States
  Connect »

Kaiser Permanente-Irvine

Irvine, CA United States
  Connect »

Kaiser Permanente-Cadillac

Los Angeles, CA United States
  Connect »

Kaiser Permanente-Modesto

Modesto, CA United States
  Connect »

Kaiser Permanente - Panorama City

Panorama City, CA United States
  Connect »

Kaiser Permanente-Riverside

Riverside, CA United States
  Connect »

Kaiser Permanente - Sacramento

Sacramento, CA United States
  Connect »

Kaiser Permanente-San Marcos

San Marcos, CA United States
  Connect »

Kaiser Permanente-Stockton

Stockton, CA United States
  Connect »

Kaiser Permanente-Vallejo

Vallejo, CA United States
  Connect »

Kaiser Permanente-Walnut Creek

Walnut Creek, CA United States
  Connect »

Penrose-Saint Francis Healthcare

Colorado Springs, CO United States
  Connect »

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, CO United States
  Connect »

Kaiser Permanente-Rock Creek

Lafayette, CO United States
  Connect »

McKee Medical Center

Loveland, CO United States
  Connect »

Yale University

New Haven, CT United States
  Connect »

Beebe Health Campus

Rehoboth Beach, DE United States
  Connect »

Nanticoke Memorial Hospital

Seaford, DE United States
  Connect »

Mount Sinai Medical Center

Miami Beach, FL United States
  Connect »

Moffitt Cancer Center

Tampa, FL United States
  Connect »

John B Amos Cancer Center

Columbus, GA United States
  Connect »

Queen's Medical Center

Honolulu, HI United States
  Connect »

Kootenai Medical Center

Coeur d'Alene, ID United States
  Connect »

Kootenai Cancer Clinic

Sandpoint, ID United States
  Connect »

Illinois CancerCare-Carthage

Carthage, IL United States
  Connect »

Centralia Oncology Clinic

Centralia, IL United States
  Connect »

Northwestern University

Chicago, IL United States
  Connect »

Carle on Vermilion

Danville, IL United States
  Connect »

Crossroads Cancer Center

Effingham, IL United States
  Connect »

Illinois CancerCare-Galesburg

Galesburg, IL United States
  Connect »

Illinois CancerCare-Princeton

Princeton, IL United States
  Connect »

IU Health North Hospital

Carmel, IN United States
  Connect »

IU Health Methodist Hospital

Indianapolis, IN United States
  Connect »

Sidney and Lois Eskenazi Hospital

Indianapolis, IN United States
  Connect »

Broadlawns Medical Center

Des Moines, IA United States
  Connect »

Mercy Medical Center-West Lakes

West Des Moines, IA United States
  Connect »

Hays Medical Center

Hays, KS United States
  Connect »

Lawrence Memorial Hospital

Lawrence, KS United States
  Connect »

Via Christi Hospital-Pittsburg

Pittsburg, KS United States
  Connect »

Flaget Memorial Hospital

Bardstown, KY United States
  Connect »

Saint Joseph Hospital East

Lexington, KY United States
  Connect »

Baptist Health Louisville

Louisville, KY United States
  Connect »

Mary Bird Perkins Cancer Center

Baton Rouge, LA United States
  Connect »

Ochsner Health Center-Summa

Baton Rouge, LA United States
  Connect »

Robert Veith MD LLC

Metairie, LA United States
  Connect »

Bronson Battle Creek

Battle Creek, MI United States
  Connect »

Saint Joseph Mercy Brighton

Brighton, MI United States
  Connect »

Saint Joseph Mercy Chelsea

Chelsea, MI United States
  Connect »

Weisberg Cancer Treatment Center

Farmington Hills, MI United States
  Connect »

Hurley Medical Center

Flint, MI United States
  Connect »

West Michigan Cancer Center

Kalamazoo, MI United States
  Connect »

Sparrow Hospital

Lansing, MI United States
  Connect »

Saint Mary Mercy Hospital

Livonia, MI United States
  Connect »

Monroe Cancer Center

Monroe, MI United States
  Connect »

Hope Cancer Center

Pontiac, MI United States
  Connect »

Saint Joseph Mercy Oakland

Pontiac, MI United States
  Connect »

Saint Mary's of Michigan

Saginaw, MI United States
  Connect »

Marie Yeager Cancer Center

Saint Joseph, MI United States
  Connect »

Munson Medical Center

Traverse City, MI United States
  Connect »

Metro Health Hospital

Wyoming, MI United States
  Connect »

Unity Hospital

Fridley, MN United States
  Connect »

Abbott-Northwestern Hospital

Minneapolis, MN United States
  Connect »

Hennepin County Medical Center

Minneapolis, MN United States
  Connect »

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, MN United States
  Connect »

Rice Memorial Hospital

Willmar, MN United States
  Connect »

Truman Medical Center

Kansas City, MO United States
  Connect »

Bozeman Deaconess Hospital

Bozeman, MT United States
  Connect »

Great Falls Clinic

Great Falls, MT United States
  Connect »

Community Medical Hospital

Missoula, MT United States
  Connect »

CHI Health Saint Francis

Grand Island, NE United States
  Connect »

Ann M Wierman MD LTD

Las Vegas, NV United States
  Connect »

Wayne Memorial Hospital

Goldsboro, NC United States
  Connect »

Cone Health Cancer Center

Greensboro, NC United States
  Connect »

Riverside Methodist Hospital

Columbus, OH United States
  Connect »

Grant Medical Center

Columbus, OH United States
  Connect »

Doctors Hospital

Columbus, OH United States
  Connect »

Kettering Medical Center

Kettering, OH United States
  Connect »

Marietta Memorial Hospital

Marietta, OH United States
  Connect »

Hillcrest Hospital Cancer Center

Mayfield Heights, OH United States
  Connect »

Knox Community Hospital

Mount Vernon, OH United States
  Connect »

Licking Memorial Hospital

Newark, OH United States
  Connect »

Southern Ohio Medical Center

Portsmouth, OH United States
  Connect »

North Coast Cancer Care

Sandusky, OH United States
  Connect »

Saint Ann's Hospital

Westerville, OH United States
  Connect »

UHHS-Westlake Medical Center

Westlake, OH United States
  Connect »

Kaiser Permanente Northwest

Portland, OR United States
  Connect »

Geisinger Medical Center

Danville, PA United States
  Connect »

Riddle Memorial Hospital

Media, PA United States
  Connect »

Paoli Memorial Hospital

Paoli, PA United States
  Connect »

Community Medical Center

Scranton, PA United States
  Connect »

Lankenau Medical Center

Wynnewood, PA United States
  Connect »

Gibbs Cancer Center-Gaffney

Gaffney, SC United States
  Connect »

Saint Francis Hospital

Greenville, SC United States
  Connect »

University Medical Center

Lubbock, TX United States
  Connect »

Sandra L Maxwell Cancer Center

Cedar City, UT United States
  Connect »

Skagit Valley Hospital

Mount Vernon, WA United States
  Connect »

Saint Mary's Medical Center

Huntington, WV United States
  Connect »

Aurora Health Center-Fond du Lac

Fond Du Lac, WI United States
  Connect »

Aurora Cancer Care-Grafton

Grafton, WI United States
  Connect »

Aurora BayCare Medical Center

Green Bay, WI United States
  Connect »

UW Cancer Center Johnson Creek

Johnson Creek, WI United States
  Connect »

Holy Family Memorial Hospital

Manitowoc, WI United States
  Connect »

Marshfield Clinic

Marshfield, WI United States
  Connect »

Marshfield Medical Center

Marshfield, WI United States
  Connect »

Aurora Cancer Care-Milwaukee

Milwaukee, WI United States
  Connect »

Aurora Sinai Medical Center

Milwaukee, WI United States
  Connect »

ProHealth D N Greenwald Center

Mukwonago, WI United States
  Connect »

Green Bay Oncology - Oconto Falls

Oconto Falls, WI United States
  Connect »

Aurora Cancer Care-Racine

Racine, WI United States
  Connect »

Billings Clinic-Cody

Cody, WY United States
  Connect »

Welch Cancer Center

Sheridan, WY United States
  Connect »

Kaiser Permanente-Fontana

Fontana, CA United States
  Connect »

City of Hope Mission Hills

Mission Hills, CA United States
  Connect »

Kaiser Permanente-Woodland Hills

Woodland Hills, CA United States
  Connect »

Saint Joseph Mercy Canton

Canton, MI United States
  Connect »

Valley Hospital

Ridgewood, NJ United States
  Connect »

Indu and Raj Soin Medical Center

Beavercreek, OH United States
  Connect »

Kaiser San Rafael-Gallinas

San Rafael, CA United States
  Connect »

Parkview Hospital Randallia

Fort Wayne, IN United States
  Connect »

Mercy Health Mercy Campus

Muskegon, MI United States
  Connect »

Lakeland Hospital Niles

Niles, MI United States
  Connect »

Capital Region Southwest Campus

Jefferson City, MO United States
  Connect »

Armes Family Cancer Center

Findlay, OH United States
  Connect »

Blanchard Valley Hospital

Findlay, OH United States
  Connect »

Orion Cancer Care

Findlay, OH United States
  Connect »

Camden Clark Medical Center

Parkersburg, WV United States
  Connect »

HSHS Saint Nicholas Hospital

Sheboygan, WI United States
  Connect »