Expanded Treatment Protocol With LDK378 in ALK(+) NSCLC

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

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

Clinical Trial Details — Status: No longer available

Administrative data

• NCT number: NCT01947608
• Other study ID #: CLDK378A2402
• Status: No longer available

Study information

• Verified date: December 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: No longer available
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• LDK378
750 mg. orally

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Córdoba	Cordoba
Colombia	Novartis Investigative Site	Cali	Valle Del Cauca
Colombia	Novartis Investigative Site	Monteria
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Kowloon
India	Novartis Investigative Site	Delhi
Jordan	Novartis Investigative Site	Amman
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Gyeonggi do	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Mexico	Novartis Investigative Site	Ciudad De Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico D F	Distrito Federal
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Taguig City	Metro Manila
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
United States	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia
United States	Peachtree Hematology/Oncology Consultants	Atlanta	Georgia
United States	Johns Hopkins Bayview Hospital	Baltimore	Maryland
United States	Massachusetts General Hospital Mass General	Boston	Massachusetts
United States	Ironwood Cancer and Research Centers	Chandler	Arizona
United States	Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Banner MDACC	Gilbert	Arizona
United States	Western Regional Medical Center, Inc.	Goodyear	Arizona
United States	Indiana University Health Goshen Center for Cancer	Goshen	Indiana
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Moores UCSD Cancer Center	La Jolla	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Advanced Medical Specialties	Miami	Florida
United States	Eastern Connecticut Hematology & Oncology Associates	Norwich	Connecticut
United States	Mercy Clinic Oklahoma Communities Mercy Oncology	Oklahoma City	Oklahoma
United States	Nebraska Cancer Specialist/Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Maryland Oncology Hematology, P.A.	Rockville	Maryland
United States	University of Utah / Huntsman Cancer Institute	Salt Lake City	Utah
United States	St Joseph Heritage Healthcare	Santa Rosa	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Colombia,  Hong Kong,  India,  Jordan,  Korea, Republic of,  Mexico,  Philippines,  Thailand,