Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Expanded Treatment Protocol With LDK378 in ALK(+) NSCLC

Expanded access is currently available for this treatment.
Verified October 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01947608
First received: September 17, 2013
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

Novartis-sponsored, open-label, multi-center, interventional ETP to provide LDK378 to patients with ALK (+)NSCLC, who have been pre-treated with an ALK inhibitor; except in countries where ALK inhibitors are not approved or available. The protocol will further evaluate the safety of LDK378 in patients with ALK(+) NSCLC.


Condition Intervention
Non-small Cell Lung Cancer (NSCLC)
Drug: LDK378

Study Type: Expanded Access     What is Expanded Access?
Official Title: An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Oral LDK378 in Adult Patients With Non-small Cell Lung Cancer (NSCLC) Characterized by ALK Positivity

Resource links provided by NLM:


Further study details as provided by Novartis:

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (patients eligible for inclusion in this early treatment protocol have to meet all of the following criteria):

  1. Histologically or cytologically confirmed diagnosis of NSCLC that demonstrates ALK positivity as assessed by approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test. If documentation of ALK positivity is not available, the test to confirm ALK positivity must be performed according to the above criterion, using a new tumor biopsy obtained prior to the first dose of ETP treatment (LDK378).
  2. Stage IIIB or IV NSCLC patient with documented disease progression at enrollment, and who does not qualify or have access to LDK378 through a clinical trial.
  3. Age 18 years or older at the time of informed consent.
  4. WHO performance status 0-3.
  5. Patients who have been pre-treated with an ALK inhibitor for locally advanced or metastatic NSCLC. Patients may be enrolled without prior exposure to an ALK inhibitor in countries where ALK inhibitors are not approved or available. Exposure to prior chemotherapy is not required.
  6. Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2 (CTCAE v 4.03), provided that concomitant medication is given prior to initiation of treatment with LDK378. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
  7. The following laboratory criteria have been met:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Hemoglobin (Hgb) ≥ 8 g/dL
    • Platelets ≥ 75 x 109/L
    • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
    • Aspartate transaminase (AST) < 3.0 x ULN, except for patients with liver metastasis, who are only included if AST < 5 x ULN; alanine transaminase (ALT) < 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 5 x ULN.
    • Calculated or measured creatinine clearance (CrCL) ≥ 30 mL/min
  8. Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:

    • Potassium ≥ LLN
    • Magnesium ≥ LLN
    • Phosphorus ≥ LLN
    • Total calcium (corrected for serum albumin) ≥ LLN
  9. Written informed consent for the ETP protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
  10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other ETP procedures.

Exclusion Criteria (patients eligible for this ETP must not meet any of the following criteria):

  1. Patients with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
  2. Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to ETP entry to manage CNS symptoms.
  3. Prior therapy with LDK378.
  4. The patient is less than 5 half-lives from prior ALK inhibitor or targeted therapy (for adequate wash-out) without recovery from treatment toxicities to ≤ grade 1 or to their pretreatment levels.
  5. Chemotherapy or an investigational therapy ≤ 3 weeks prior to starting the LDK378 treatment who have not recovered from side effects of such treatment toxicities to ≤ grade 2 or to their pre- treatment toxicities levels, with the exception of liver and cardiac functions which must be ≤ grade 1.
  6. Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤ 2 weeks prior to starting the LDK378 treatment or have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting LDK378 treatment is allowed.
  7. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting LDK378 treatment or who have not recovered from side effects of such procedures. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery, and patients can be enrolled in the ETP ≥ 2 weeks after the procedure.
  8. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
  9. Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
  10. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:

    • unstable angina within 6 months prior to screening;
    • myocardial infarction within 6 months prior to screening;
    • history of documented congestive heart failure (New York Heart Association functional classification III-IV);
    • uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication -
    • initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;
    • ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication;
    • other cardiac arrhythmia not controlled with medication;
    • corrected QTc > 450 msec using Fridericia correction on the screening ECG
  11. Impaired GI function or GI disease that may alter absorption of LDK378 or inability to swallow up to five LDK378 capsules daily
  12. Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the ETP.
  13. Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of the ETP participation (see Appendix 1: Tables 14-1, Table 14-2, Table 14-3, and Table 14-4):

    • Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)
    • Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
    • Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
    • Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban).
    • Unstable or increasing doses of corticosteroids
    • enzyme-inducing anticonvulsive agents
    • herbal supplements
  14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  15. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment.

    In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

    Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

  16. Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment. Male patients for 3 months should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01947608

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Hide Study Locations
Locations
United States, Alabama
Alabama Oncology
Birmingham, Alabama, United States, 35211
Contact    205-939-7181      
Principal Investigator: James Lasker         
United States, Arizona
Ironwood Cancer and Research Centers
Chandler, Arizona, United States, 85224
Contact    480-855-2225      
Principal Investigator: Sujith R. Kalmadi         
Banner MDACC
Gilbert, Arizona, United States, 85234
Contact    480-256-3333      
Principal Investigator: Klaus Wagner         
Western Regional Medical Center, Inc.
Goodyear, Arizona, United States, 85338
Contact    602-358-8400      
Principal Investigator: Glen Weiss         
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
Contact    479-587-1700      
Principal Investigator: Eric S. Schaefer         
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
Contact    626-359-8111      
Principal Investigator: Marianna Koczywas         
Moores UCSD Cancer Center
La Jolla, California, United States, 92093
Contact    858-822-6267      
Principal Investigator: Lyudmila Bazhenova         
Pacific Shores Medical Group
Long Beach, California, United States, 90813
Contact    562-590-0345      
Principal Investigator: Andre K. Liem         
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States, 90073
Contact    310-478-3711      
Principal Investigator: Matthew Rettig         
Redwood Regional Medical Group - Santa Rosa
Santa Rosa, California, United States, 94503
Contact    707-525-3930      
Principal Investigator: Ian Anderson         
Stanford University
Stanford, California, United States, 94305-5203
Contact    650-725-3973      
Principal Investigator: Heather Ann Wakelee         
United States, Colorado
Memorial Medical Center
Colorado Springs, Colorado, United States, 80909
Contact    719-365-6568      
Principal Investigator: Robert Hoyer         
Denver Health Medical Center
Denver, Colorado, United States, 80204-4507
Contact    303-436-5789      
Principal Investigator: Ana Oton         
St Mary's Cancer Center
Grand Junction, Colorado, United States, 81501
Contact    970-298-7125      
Principal Investigator: Mark Hancock         
Banner Health Clinic Oncology/Hematolgy
Greeley, Colorado, United States, 80631
Contact    970-378-3894      
Principal Investigator: Ariel Soriano         
United States, Connecticut
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States, 06360
Contact    860-886-8362      
Principal Investigator: Dennis E. Slater         
Cancer Centers of Connecticut
Southington, Connecticut, United States, 06489
Principal Investigator: Peter Byeff         
United States, District of Columbia
MedStar Clinical Res Institute at Washington Hospital Center
Washington, District of Columbia, United States, 20010
Contact    202-877-9163      
Principal Investigator: Suman B. Rao         
United States, Florida
Advanced Medical Specialties
Miami, Florida, United States, 33176
Contact    305-595-2141      
Principal Investigator: Paul Kaywin         
Cleveland Clinic Florida
Weston, Florida, United States, 33331
Contact    954-659-6213      
Principal Investigator: Bruno Bastos         
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Contact    404-712-2587      
Principal Investigator: Suchita Pakkala         
Peachtree Hematology/Oncology Consultants
Atlanta, Georgia, United States, 30309
Contact    512-421-4163      
Principal Investigator: Charles Henderson         
The Medical Center, Inc. John B. Amos Cancer Center
Columbus, Georgia, United States, 31901
Contact    706-571-1050      
Principal Investigator: Andrew Pippas         
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Contact    312-695-1379      
Principal Investigator: Jyoti Patel         
Rush University Medical Center
Chicago, Illinois, United States, 60612
Contact    312-942-8011      
Principal Investigator: Mary J Fidler         
Oncology Specialists, SC
Park Ridge, Illinois, United States, 60068-0736
Contact    866-611-1991      
Principal Investigator: Navkiranjit Gill         
SwedishAmerican Regional Cancer Center
Rockford, Illinois, United States, 61114
Contact    779-696-9400      
Principal Investigator: William Schulz         
Carle Foundation Hospital/ Carle Cancer Center
Urbana, Illinois, United States, 61801
Contact    217-383-6828      
Principal Investigator: James Egner         
United States, Indiana
Indiana University Health Goshen Center for Cancer
Goshen, Indiana, United States, 46526
Contact    574-535-2888      
Principal Investigator: Ebenezer Kio         
Memorial Hospital of South Bend, Inc.
South Bend, Indiana, United States, 46601
Contact    574-647-1100      
Principal Investigator: Thomas Reid         
United States, Kansas
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Contact    913-498-7892      
Principal Investigator: Joseph Stilwill         
Cotton O'Neil Clinical Resaerch
Topeka, Kansas, United States, 66606
Contact    785-270-4850      
Principal Investigator: Daniel Einsphar         
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
Contact    913-588-0789      
Principal Investigator: Heather Male         
United States, Maryland
Johns Hopkins Bayview Hospital
Baltimore, Maryland, United States, 21224
Contact    410-550-1117      
Principal Investigator: Rodrigo Erlich         
Associates in Oncology/Hematology, P.C.
Rockville, Maryland, United States, 20850
Contact    301-424-6231      
Principal Investigator: Nicholas Farrell         
United States, Massachusetts
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States, 02114
Contact    617-632-2408      
Principal Investigator: Alice Shaw         
Lahey Clinic
Burlington, Massachusetts, United States, 01805
Contact    781-744-2500      
Principal Investigator: Paul Hesketh         
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Contact    800-527-6266      
Principal Investigator: Shirish M. Gadgeel         
St. Joseph Mercy Health System
Ypsilanti, Michigan, United States, 48197
Contact    734-712-5396      
Principal Investigator: Philip Stella         
United States, Minnesota
Southdale Cancer Clinic
Edina, Minnesota, United States, 55432-2129
Contact    952-836-3645      
Principal Investigator: Priya Kumar         
Mayo Clinic - Rochester
Rochester, Minnesota, United States, 55905
Contact    507-284-2511      
Principal Investigator: Julian R. Molina         
United States, Mississippi
Jackson Oncology Associates
Jackson, Mississippi, United States, 39202
Contact    601-974-5547      
Principal Investigator: Bobby L. Graham         
United States, Nebraska
Nebraska Hematology-Oncology PC
Lincoln, Nebraska, United States, 68506
Principal Investigator: Mark Hutchins         
Nebraska Cancer Specialist/Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Contact    402-991-8070      
Principal Investigator: Gamini S Soori         
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Contact    201-996-2000      
Principal Investigator: Martin E. Gutierrez         
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Contact    732-235-7457      
Principal Investigator: Mark N. Stein         
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
Contact    212-420-4111      
Principal Investigator: Ben Levy         
United States, Ohio
Akron City Hospital Summa Health System
Akron, Ohio, United States, 44304-1619
Contact    330-375-3000      
Principal Investigator: Jennifer E. Payne         
United States, Oklahoma
Mercy Clinic Oklahoma Communities Mercy Oncology
Oklahoma City, Oklahoma, United States, 73120-9391
Contact    954-659-5579      
Principal Investigator: Jess F. Armor         
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Contact    503-494-9000      
Principal Investigator: Ariel Loopez-Chavez         
United States, Pennsylvania
Lehigh Valley Hospital
Allentown, Pennsylvania, United States, 18103
Contact    610-402-9830      
Principal Investigator: Eliot Friedman         
Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States, 17325
Contact    717-334-4033      
Principal Investigator: Satish Shah         
Lancaster Cancer Center
Lancaster, Pennsylvania, United States, 17601
Contact    717-291-1313      
Principal Investigator: H. Peter Degreen         
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 196111
Contact    215-728-3545      
Principal Investigator: Ranee Mehra         
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
Contact    412-359-3802      
Principal Investigator: Moses Raj         
Ambington Hematology/Oncology Associates
Willow Grove, Pennsylvania, United States, 19090
Contact    215-706-2034      
Principal Investigator: Peter Pickens         
United States, South Carolina
Medical University of South Carolina -Hollings Cancer Center
Charleston, South Carolina, United States, 29425
Contact    843-792-1415      
Principal Investigator: Keisuke Shirai         
United States, Tennessee
Erlanger Medical Center
Chattanooga, Tennessee, United States, 37403
Contact    423-778-7537      
Principal Investigator: Robert Graham         
The Jones Clinic
Germantown, Tennessee, United States, 38138
Contact    901-685-5969      
Principal Investigator: Clyde Jones         
Tennessee Cancer Specialists Center for Biomedical Research
Knoxville, Tennessee, United States, 37909
Contact    865-934-2675      
Principal Investigator: Russell F DeVore         
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Contact    214-645-6488      
Principal Investigator: Joan H. Schiller         
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77021
Contact    713-741-3803      
Principal Investigator: Shan Guo         
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Contact    713-745-3357      
Principal Investigator: George R. Blumenschein         
United States, Utah
Northern Utah Cancer Associates
Ogden, Utah, United States, 84403
Contact    801-398-2836      
Principal Investigator: Harold Johnson         
University of Utah / Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112-5820
Contact    801-585-5318      
Principal Investigator: Sunil Sharma         
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Contact    206-288-2171      
Principal Investigator: Christina Baik         
University of Washington Medical Center
Seattle, Washington, United States, 98195
Contact    206-543-3608      
Principal Investigator: Daniel Morganzstern         
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705-2397
Principal Investigator: Ticiana Leal         
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1431FWO
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1426ANZ
Novartis Investigative Site
Córdoba, Cordoba, Argentina, 5000
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Hongkong, Hong Kong
India
Novartis Investigative Site
New Delhi, Delhi, India, 110076
Novartis Investigative Site
New Delhi, Delhi, India, 110 060
Novartis Investigative Site
Karamsad, Gujarat, India, 388 325
Novartis Investigative Site
Bangalore, Karnataka, India, 560 095
Mexico
Novartis Investigative Site
Mexico, D.F., Distrito Federal, Mexico, 06760
Novartis Investigative Site
México, Distrito Federal, Mexico, 14080
Novartis Investigative Site
Chihuahua, Mexico, 31328
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Bangkok, Thailand, 10400
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01947608     History of Changes
Other Study ID Numbers: CLDK378A2402
Study First Received: September 17, 2013
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014