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(Novartis Signature) Modular phase II study to link targeted therapy to patients with pathway activated tumors: Module 4 - LGX818 for patients with BRAFV600 mutated tumors

Conditions

Bladder | Brain and Nervous System | Breast - Female | Esophagus | Eye and Orbit | Kidney | Larynx | Lip, Oral Cavity and Pharynx | Liver | Lung | Melanoma, skin | Other Skin | Ovary | Pancreas | Prostate | Rectum | Small Intestine | Soft Tissue | Stomach

Trial Phase

Phase II

Trial Purpose and Description

Trial Purpose

To assess clinical benefit associated with LGX818 treatment based on local investigator assessment.


Participation Guidelines

Age:
18 Years and older
Gender:
Both

Eligibility Criteria

Inclusion Criteria:

  1. Patient has provided a signed study Informed Consent Form prior to any screening procedure
  2. Patient is &ge 18 years of age on the day of consenting to the study
  3. Patient has a confirmed diagnosis of a select solid tumor (except melanoma and colorectal cancer (CRC)) or hematological malignancy and is in need of treatment because of radiologic progression or relapse. Additional tumor types may be excluded during the course of the study at the discretion of Novartis.
  4. Patient is in need of treatment because of progression or relapse defined as: &bull radiological progression for solid tumor and lymphoma &bull for hematologic malignancies, measureable progression or relapse by appropriate criteria
  5. Patient must have been pre-identified as having a tumor with a BRAFV600 mutation. The qualifying alteration must be assessed and reported by a CLIA-certified laboratory.
  6. Patient must have archival tissue available for submission to allow for molecular testing related to pathway activation. If the tissue is not available or not of sufficient quantity the patient must be willing to undergo a fresh tumor biopsy to allow for this analysis. The sample must be submitted prior to first study dose unless agreed upon between Novartis and the investigator.
  7. Leukemia only: Relapsed/refractory leukemia for which no standard therapy options are anticipated to result in a durable remission:
    &bull Acute myelogenous leukemia (AML) by World Health Organization (WHO)
    classification or acute lymphoblastic leukemia (ALL) relapsed or refractory to
    standard chemotherapy unsuitable for standard chemotherapy or unwilling to
    undergo standard chemotherapy. Philadelphia chromosome (Ph) positive ALL
    eligible if failed prior tyrosine-kinase inhibitor therapy.
    &bull Age > 60 years with AML not candidates for or have refused standard
    chemotherapy, excluding patients with acute promyelocytic leukemia (APL) or
    with favorable cytogenetic abnormalities [inv16, t(821)].
    &bull For patients with Chronic Myeloid Leukemia (CML) only accelerated and blast
    phase CML will be allowed.

Exclusion Criteria:

1. Patients who have received prior treatment with LGX818
2. Patients with a known hypersensitivity to LGX818 or to its excipients
3. Patients with primary CNS tumor or CNS tumor involvement. However, patients with
metastatic CNS tumors may participate in this study if the patient meets criteria a-e:
a. 4 weeks from prior therapy completion (including radiation and/or surgery)
b. Clinically stable with respect to the CNS tumor at the time of study entry
c. Not receiving steroid therapy
d. Not receiving anti-convulsive medications (that were started for brain metastases)
e. Patient with no leptomeningeal involvement
4. Patients with diarrhea &ge CTCAE grade 2
5. Patients with neuropathy &ge CTCAE grade 2
6. Patients with acute or chronic pancreatitis.
7. Patients with external biliary drains.
8. Patients with impaired cardiac function or clinically significant cardiac diseases, including
any of the following:
a. History or presence of serious uncontrolled ventricular arrhythmias or atrial
fibrillation
b. Clinically significant resting bradycardia
c. LVEF < 45% as determined by MUGA scan or ECHO
d. Any of the following within 6 months prior to starting study drug: myocardial
infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG),
congestive heart failure (CHF) requiring treatment, cerebrovascular accident (CVA),
transient ischemic Attack (TIA), deep vein thrombosis, or pulmonary embolism e. Uncontrolled hypertension defined by a SBP &ge 160 mm Hg and/or DBP &ge 100 mm Hg,
with or without anti-hypertensive medication(s). Initiation or adjustment of
antihypertensive medication(s) is allowed prior to study entry.
f. QTcF >480 msec on screening ECGs
9. Patients with uncontrolled diabetes mellitus.
10. Patient has graft-versus-host disease (GVHD)

Sponsor:
Novartis Pharmaceuticals
Dates:
07/21/2014
Last Updated:
Study HIC#:
1406014167