Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

ACTIVE NOT RECRUITING

NCT03737994

PHASE2

Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, 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. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.

Official title: A Biomarker-Driven Protocol for Previously Treated ALK-Positive Non-Squamous NSCLC Patients: The NCI-NRG ALK Protocol

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2019-07-25

Completion Date

2027-03-18

Last Updated

2026-04-07

Healthy Volunteers

Conditions

Lung Non-Squamous Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8

Interventions

DRUG

Alectinib

Given PO

DRUG

Brigatinib

Given PO

DRUG

Carboplatin

Given IV

DRUG

Ceritinib

Given PO

DRUG

Cisplatin

Given IV

DRUG

Crizotinib

Given PO

DRUG

Ensartinib

Given PO

DRUG

Lorlatinib

Given PO

DRUG

Pemetrexed

Given IV

Inclusion Criteria: * PRIOR TO STEP 1 REGISTRATION * Patients must have histologically or cytologically confirmed stage IV ALK-positive non-squamous non-small cell lung carcinoma (NSCLC) (includes M1a, M1b, M1c stage disease, American Joint Committee on Cancer \[AJCC\] 8th edition). ALK rearrangement must have been demonstrated by a Food and Drug Administration (FDA) approved assay (Vysis fluorescence in situ hybridization \[FISH\] or Ventana immunohistochemistry \[IHC\]) or by next generation sequencing (NGS) * Patient must be willing and able to undergo a fresh biopsy or if patient has a biopsy after progression on current tyrosine-kinase inhibitor (TKI) within 3 months of study enrollment (and has continued TKI for clinical benefit per treating physician) this tissue may be used. Must have sufficient tissue * Patient must have progressive disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after one second generation ALK inhibitor, including LDK378 (ceritinib), alectinib, ensartinib, and brigatinib (may not have received more than one second-generation ALK inhibitor). Patient may have received prior crizotinib; however, the second generation ALK inhibitor received must be the last treatment given prior to study enrollment * Prior lorlatinib (third-generation ALK inhibitor) is not allowed * Prior chemotherapy is not allowed except for one prior cycle received at the time of original diagnosis of metastatic NSCLC with no evidence of disease progression following the cycle. NOTE: prior adjuvant or neoadjuvant chemotherapy is allowed if last dose was received more than 12 months prior to enrollment * The patient or a legally authorized representative must provide study-specific informed consent prior to Step 1 Registration * PRIOR TO STEP 2 REGISTRATION * Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 (within 28 days prior to step 2 registration) * Platelets \>= 100,000 cells/mm\^3 (within 28 days prior to step 2 registration) * Estimated creatinine clearance \>= 60 mL/min by the Cockcroft Gault formula (within 28 days prior to step 2 registration) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's syndrome) (within 28 days prior to step 2 registration) * Aspartate aminotransferase (AST) =\< 2.5 x ULN; =\< 5 x ULN if liver metastases are present (within 28 days prior to step 2 registration) * Alanine aminotransferase (ALT) =\< 2.5 x ULN; =\< 5 x ULN if liver metastases are present (within 28 days prior to step 2 registration) * Patients with asymptomatic treated or untreated brain metastases are eligible. Treated brain metastases are eligible as long as patients have measurable disease outside the brain according to RECIST 1.1. Patients must be on a stable or decreasing dose of steroids for at least 7 days prior to step 2 registration. Anticonvulsants are allowed as long as the patient is neurologically stable and not deteriorating * Patients enrolled with asymptomatic brain metastases (mets) must have at least one measurable target extracranial lesion according to RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Acute effects of any prior therapy resolved to baseline severity or to Common Terminology Criteria for Adverse Events (CTCAE) grade =\< 1 (except for alopecia, hearing loss) * Not taking any medications that may interact with selected study medication based on stratification * Patients must be able to take oral medications (i.e. swallow whole tablets/capsules) * All females of childbearing potential must have a blood test or urine study within 14 days prior to Step 2 Registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from ALK inhibitors and the unknown risk. Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study Exclusion Criteria: * Major surgery within 2 weeks of study entry. Minor surgical procedures (e.g., port insertion, pleurex catheter placement) are allowed and all wounds must not show signs of infection or draining * Palliative RT (\< 10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 1 week prior to study entry. Whole brain RT or other palliative RT must have been completed at least 2 weeks prior to study entry * Prior dose of next generation ALK inhibitor (LDK378 \[ceritinib\], alectinib, ensartinib, lorlatinib) within 5 days prior to step 2 registration. Prior dose of brigatinib within 7 days prior to step 2 registration * History of interstitial lung disease or interstitial fibrosis, including a history of pneumonitis, obliterative bronchiolitis, pulmonary fibrosis. Patients with a history of prior radiation pneumonitis are not excluded * Active inflammatory gastrointestinal disease (such as Crohns, ulcerative colitis), chronic diarrhea, symptomatic diverticular disease, or any gastrointestinal disease that would affect the absorption of oral medications or increase the risk of toxicity * Clinically significant cardiovascular abnormalities, as determined by the treating/registering physician, such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months * Active and clinically significant bacterial, fungal, or viral infection * Patients with active or chronic pancreatitis based on lipase elevation, symptoms, and radiographic findings * Other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug * Patients must not plan to receive any other investigational agents during the course of therapy * Patients with active malignancy other than ALK-positive non-squamous NSCLC within the last 2 years are excluded (note: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer treated with curative intent, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for 2 years are eligible) * No chemotherapy and/or immunotherapy allowed after step 1 registration

Locations (491)

CTCA at Western Regional Medical Center

Goodyear, Arizona, United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Mercy Hospital Fort Smith

Fort Smith, Arkansas, United States

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

Kaiser Permanente-Anaheim

Anaheim, California, United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

Mission Hope Medical Oncology - Arroyo Grande

Arroyo Grande, California, United States

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Kaiser Permanente Dublin

Dublin, California, United States

21st Century Oncology - El Segundo

El Segundo, California, United States

Kaiser Permanente-Fontana

Fontana, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Fresno Cancer Center

Fresno, California, United States

Kaiser Permanente-Fresno

Fresno, California, United States

Kaiser Permanente South Bay

Harbor City, California, United States

Kaiser Permanente-Irvine

Irvine, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Kaiser Permanente West Los Angeles

Los Angeles, California, United States

Kaiser Permanente-Modesto

Modesto, California, United States

Kaiser Permanente Oakland-Broadway

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Kaiser Permanente-Ontario

Ontario, California, United States

Kaiser Permanente - Panorama City

Panorama City, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States

Kaiser Permanente-Redwood City

Redwood City, California, United States

Kaiser Permanente-Richmond

Richmond, California, United States

Kaiser Permanente-Riverside

Riverside, California, United States

Rohnert Park Cancer Center

Rohnert Park, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States

Kaiser Permanente Downtown Commons

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

South Sacramento Cancer Center

Sacramento, California, United States

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States

Kaiser Permanente-San Diego Mission

San Diego, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Pacific Central Coast Health Center-San Luis Obispo

San Luis Obispo, California, United States

Kaiser Permanente-San Marcos

San Marcos, California, United States

Kaiser Permanente-San Rafael

San Rafael, California, United States

Kaiser San Rafael-Gallinas

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Kaiser Permanente-Stockton

Stockton, California, United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

Kaiser Permanente-Woodland Hills

Woodland Hills, California, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

AdventHealth Porter

Denver, Colorado, United States

CommonSpirit Cancer Center Mercy

Durango, Colorado, United States

Mercy Medical Center

Durango, Colorado, United States

Mountain Blue Cancer Care Center

Golden, Colorado, United States

Rocky Mountain Cancer Centers-Lakewood

Lakewood, Colorado, United States

Saint Anthony Hospital

Lakewood, Colorado, United States

AdventHealth Littleton

Littleton, Colorado, United States

Longmont United Hospital

Longmont, Colorado, United States

Rocky Mountain Cancer Centers-Longmont

Longmont, Colorado, United States

AdventHealth Parker

Parker, Colorado, United States

Rocky Mountain Cancer Centers-Parker

Parker, Colorado, United States

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

Rocky Mountain Cancer Centers - Pueblo

Pueblo, Colorado, United States

Rocky Mountain Cancer Centers-Thornton

Thornton, Colorado, United States

Beebe Medical Center

Lewes, Delaware, United States

Beebe South Coastal Health Campus

Millville, Delaware, United States

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Beebe Health Campus

Rehoboth Beach, Delaware, United States

TidalHealth Nanticoke / Allen Cancer Center

Seaford, Delaware, United States

Christiana Care Health System-Wilmington Hospital

Wilmington, Delaware, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

GenesisCare USA - Aventura FP

Aventura, Florida, United States

GenesisCare USA - Boca Raton FP02

Boca Raton, Florida, United States

GenesisCare USA - Boca Ration FP06

Boca Raton, Florida, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

GenesisCare USA - Key West

Key West, Florida, United States

GenesisCare USA - Lakewood Ranch

Lakewood Rch, Florida, United States

GenesisCare USA - Palm Beach Gardens

Palm Beach Gardens, Florida, United States

GenesisCare USA - Plantation

Plantation, Florida, United States

Good Samaritan Medical Center

West Palm Beach, Florida, United States

Grady Health System

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Northside Hospital

Atlanta, Georgia, United States

Northside Hospital - Duluth

Duluth, Georgia, United States

Emory Johns Creek Hospital

Johns Creek, Georgia, United States

Northside Hospital - Gwinnett

Lawrenceville, Georgia, United States

CTCA at Southeastern Regional Medical Center

Newnan, Georgia, United States

Suburban Hematology Oncology Associates - Snellville

Snellville, Georgia, United States

Hawaii Cancer Care Inc - Waterfront Plaza