Naloxegol in Treating Patients with Stage IIIB-IV Non-small Cell Lung Cancer
Inclusion Criteria
- Advanced (stage IIIB or IV) non-small cell lung cancer diagnosed by biopsy of the primary or metastatic site (American Joint Committee on Cancer 7.0)
- No known presence of known EGFR or EML4-ALK driver mutations in the tumor
- Started first-line systemic therapy of the investigator’s choice within 12 weeks prior to registration, or planning to initiate first-line systemic therapy of the investigator’s choice within 4 weeks after registration; no planned initiation of definitive (potentially curative) concurrent chemo-radiation
- No prior systemic therapy for advanced NSCLC, including chemotherapy, targeted therapy or immunotherapy (other than current treatment); prior palliative radiation permitted; prior adjuvant systemic therapy /radiation is permitted
- No more than 7 days of prior use of mixed opioid agonist/opioid antagonists or other opioid antagonists within 4 weeks before registration; patients should not receive such medications after registration and for the entire duration of study treatment
- No methadone within 4 weeks prior to registration
- Patients must have used opioid medication(s) for pain at some time in the 4 weeks prior to registration; current use of opioids (at the time of registration) and/or later during the course of the study is permitted but not required
- Expected survival > 3 months
- No concurrently active second invasive malignancies except non-melanoma skin cancer
- No history of gastrointestinal obstruction, or conditions that increase the risk of gastrointestinal obstruction, perforation, bleeding or impairment of the gastrointestinal wall; no abdominal surgery within 60 days of registration
- No acute gastrointestinal conditions, such as: obstruction, fecal impaction, obstipation, acute surgical abdomen, ongoing need for manual maneuvers to induce bowel movements (such as digital evacuation)
- No conditions that may compromise blood-brain barrier permeability (e.g., multiple sclerosis, recent brain trauma, Alzheimer’s disease, or uncontrolled seizures) * No symptomatic and untreated brain metastases; patients will be eligible for study if radiation therapy for brain metastases was completed at least 7 days prior to registration * Patients having received stereotactic radiation will be eligible if the radiation was completed at least 7 days prior to registration * Patients having undergone surgical resection of brain metastases will be eligible after they have healed and recovered from the surgical intervention sufficiently to start systemic treatment for NSCLC, as determined by a neurosurgeon * No known leptomeningeal carcinomatosis
- No history of myocardial infarction =< 6 months prior to registration; no current symptomatic congestive heart failure, uncontrolled angina, or uncontrolled cardiac arrhythmias
- No severe hepatic impairment (Child-Pugh class C) or acute liver disease
- No known serious or severe hypersensitivity reaction to naloxegol or any of its excipients
- No concurrent use of moderate/strong CYP3A4 inhibitors, or strong CYP3A4 inducers
- Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown; therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required; a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Calculated (calc.) creatinine clearance >= 60 mL/min calculated using the Cockcroft-Gault formula
- Total bilirubin =< 1.2 x upper limit of normal (ULN) unless due to Gilbert’s disease
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
Alaska
Anchorage
Fairbanks
Arizona
Kingman
Arkansas
Hot Springs
Jonesboro
California
Arroyo Grande
Burbank
Long Beach
Los Angeles
Newport Beach
Pasadena
Santa Maria
Colorado
Aurora
Boulder
Colorado Springs
Denver
Durango
Englewood
Golden
Grand Junction
Greeley
Lafayette
Lakewood
Littleton
Lone Tree
Longmont
Loveland
Parker
Pueblo
Thornton
Wheat Ridge
Connecticut
Middletown
Delaware
Lewes
Newark
Rehoboth Beach
Seaford
Wilmington
Florida
Fort Lauderdale
Hollywood
Pembroke Pines
Plant City
Saint Petersburg
Georgia
Savannah
Hawaii
Aiea
Honolulu
Lihue
Idaho
Boise
Caldwell
Coeur D'Alene
Emmett
Fruitland
Meridian
Nampa
Post Falls
Sandpoint
Twin Falls
Illinois
Aurora
Bloomington
Canton
Carbondale
Carterville
Carthage
Centralia
Chicago
Danville
Decatur
Dixon
Effingham
Eureka
Galesburg
Joliet
Kewanee
Macomb
Mattoon
O'Fallon
Ottawa
Pekin
Peoria
Peru
Princeton
River Forest
Springfield
Swansea
Urbana
Yorkville
Indiana
Mishawaka
Richmond
South Bend
Iowa
Ames
Boone
Clive
Council Bluffs
Creston
Des Moines
Fort Dodge
Jefferson
Marshalltown
Sioux City
West Des Moines
Kansas
Chanute
Dodge City
El Dorado
Fort Scott
Hays
Independence
Kingman
Lawrence
Liberal
Manhattan
McPherson
Newton
Olathe
Overland Park
Parsons
Pittsburg
Pratt
Salina
Topeka
Wellington
Westwood
Wichita
Winfield
Kentucky
Bardstown
Corbin
Elizabethtown
Lexington
London
Louisville
Morehead
Shepherdsville
Massachusetts
Beverly
Gloucester
Milford
South Weymouth
Springfield
Michigan
Ann Arbor
Battle Creek
Brighton
Canton
Caro
Chelsea
Clarkston
Dearborn
Detroit
East China
East Lansing
Escanaba
Farmington Hills
Flint
Grand Rapids
Grosse Pointe
Grosse Pointe Woods
Jackson
Kalamazoo
Lansing
Livonia
Macomb Township
Marlette
Muskegon
Niles
Norton Shores
Pontiac
Port Huron
Reed City
Rochester Hills
Roseville
Royal Oak
Saginaw
Saint Joseph
Sterling Heights
Tawas City
Traverse City
Troy
Warren
West Branch
Wyoming
Ypsilanti
Minnesota
Aitkin
Bemidji
Brainerd
Burnsville
Cambridge
Coon Rapids
Deer River
Detroit Lakes
Duluth
Edina
Fergus Falls
Fosston
Fridley
Hibbing
Maple Grove
Maplewood
Minneapolis
Monticello
New Ulm
Park Rapids
Princeton
Robbinsdale
Rochester
Saint Louis Park
Saint Paul
Sandstone
Shakopee
Stillwater
Thief River Falls
Virginia
Waconia
Willmar
Woodbury
Worthington
Wyoming
Mississippi
Columbus
Grenada
Jackson
New Albany
Oxford
Southhaven
Missouri
Bonne Terre
Cape Girardeau
Farmington
Jefferson City
Kansas City
Lee's Summit
North Kansas City
Saint Louis
Sainte Genevieve
Sullivan
Sunset Hills
Montana
Anaconda
Billings
Bozeman
Butte
Great Falls
Helena
Kalispell
Missoula
Nebraska
Grand Island
Kearney
Lincoln
Omaha
Papillion
Nevada
Carson City
Henderson
Las Vegas
Pahrump
Reno
New Hampshire
Concord
Londonderry
Manchester
New York
Auburn
Bay Shore
Buffalo
East Syracuse
Elmira
Lake Success
Rochester
Stony Brook
Syracuse
North Carolina
Clinton
Durham
Goldsboro
Henderson
Hendersonville
Jacksonville
Kenansville
Kinston
Laurinburg
Lumberton
Richlands
Salisbury
Smithfield
North Dakota
Bismarck
Fargo
Jamestown
Ohio
Beavercreek
Belpre
Boardman
Centerville
Chillicothe
Cincinnati
Columbus
Dayton
Delaware
Dublin
Findlay
Franklin
Greenville
Grove City
Kettering
Lancaster
Mansfield
Marietta
Marion
Mount Vernon
Newark
Portsmouth
Springfield
Troy
Warren
Westerville
Youngstown
Zanesville
Oklahoma
Oklahoma City
Tulsa
Oregon
Baker City
Bend
Clackamas
Coos Bay
Newberg
Ontario
Portland
Redmond
Pennsylvania
Allentown
Bethlehem
Chadds Ford
Danville
East Stroudsburg
Hazleton
Lewisburg
Lewistown
Pottsville
Scranton
Selinsgrove
State College
Wilkes-Barre
South Carolina
Boiling Springs
Clinton
Easley
Greenville
Greenwood
Greer
Seneca
South Dakota
Sioux Falls
Tennessee
Chattanooga
Hixson
Memphis
Ooltewah
Texas
Bryan
Dallas
Utah
American Fork
Cedar City
Logan
Murray
Ogden
Provo
Riverton
Saint George
Salt Lake City
Virginia
Fishersville
Washington
Aberdeen
Auburn
Bellevue
Bellingham
Bremerton
Burien
Centralia
Edmonds
Enumclaw
Everett
Federal Way
Gig Harbor
Issaquah
Kennewick
Lacey
Lakewood
Longview
Port Townsend
Poulsbo
Puyallup
Renton
Seattle
Sedro-Woolley
Shelton
Spokane
Spokane Valley
Tacoma
Vancouver
Walla Walla
Yelm
Wisconsin
Ashland
Burlington
Eau Claire
Fond Du Lac
Germantown
Grafton
Green Bay
Kenosha
Manitowoc
Marinette
Marshfield
Milwaukee
Minocqua
New Richmond
Oconto Falls
Oshkosh
Racine
Rice Lake
Sheboygan
Stevens Point
Sturgeon Bay
Summit
Two Rivers
Wausau
Wauwatosa
West Allis
Weston
Wyoming
Cheyenne
Cody
Sheridan
PRIMARY OBJECTIVES:
I. To determine feasibility and safety of long-term administration of two doses of a peripheral opioid receptor antagonist in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line systemic therapy.
SECONDARY OBJECTIVES:
I. To explore whether patients randomized to one or both of the two study drug arms have less decline in health-related quality of life (HRQoL) than patients randomized to placebo.
II. To estimate the difference in the pain levels and opioid/non-opioid analgesic requirements between patients receiving naloxegol or placebo.
III. To estimate the difference in the adverse peripheral effects of opioids (e.g. constipation, nausea/emesis, dry mouth and urinary retention) between patients receiving naloxegol or placebo.
IV. To explore whether there is a signal that naloxegol may be associated with longer progression-free survival (PFS) and overall survival (OS).
V. To evaluate the difference in discontinuation rate of systemic therapy due to adverse events (AEs) and deaths attributable to systemic therapy.
CORRELATIVE SCIENCE OBJECTIVES:
I. To examine if MOR expression or activation is a prognostic marker in advanced NSCLC, and whether its expression/activation can be used to guide pain management.
OUTLINE: Patients are randomized to 1 of 3 groups.
GROUP I (LOWER DOSE NALOXEGOL): Patients receive lower dose naloxegol orally (PO) once daily (QD) and placebo PO QD. Cycles repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
GROUP II (HIGHER DOSE NALOXEGOL): Patients receive placebo PO QD and higher dose naloxegol PO QD. Cycles repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
GROUP III (PLACEBO): Patients receive placebo PO QD. Cycles repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Trial Phase Phase II
Trial Type Supportive care
Lead Organization
Alliance for Clinical Trials in Oncology
Principal Investigator
Pankaj Gupta
- Primary ID A221504
- Secondary IDs NCI-2016-01503
- Clinicaltrials.gov ID NCT03087708