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The Safety and Efficacy Study of Vemurafenib (CT) Compared With Vemurafenib (Zelbolaf�) in Advanced Patients Harboring the V600 BRAF Mutation

Information source: Cancer Centre of Monoclonal Therapy, LLC
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Colorectal Cancer; Recurrent/Refractory BRAFV600E-mutant Gliomas; Advanced Cancers; Melanoma; Advanced BRAF-mutant Cancers

Intervention: Vemurafenib (Drug); Vemurafenib (CT) (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Cancer Centre of Monoclonal Therapy, LLC

Official(s) and/or principal investigator(s):
Viktor Lanevskij, PhD, Principal Investigator, Affiliation: Cancer Center
Viktor Lanevskij, PhD, Study Director, Affiliation: Cancer Center

Summary

The safety and efficacy study of Vemurafenib (CT) compared with Vemurafenib (Zelbolaf) Advanced patients carrying the V600E BRAF mutation.

Clinical Details

Official title: The Safety and Efficacy Study of Vemurafenib (CT) Compared With Vemurafenib (Zelbolaf) in Advanced Patients Harboring the V600 BRAF Mutation

Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Toxicities will be assessed through the NCI-Common Terminology Criteria for Adverse Events version 4.0, individually reported and summarized.

Objective response rate (ORR)

Secondary outcome: Number of Participants With Progression Free Survival (PFS)

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Signed written informed consent

- Recheck the results of histological studies and paraffin blocks

- Histologically confirmed cancer that is either Stage IIIc (unresectable) or ---Stage

IV (metastatic), and determined to be BRAF V600E or V600K mutation-positive by the local laboratory.

- Measurable tumor by physical or radiographic examination

- Subjects must not have had more than 1 previous treatment regimen with chemotherapy,

interferon, or IL-2 for metastatic melanoma

- All prior anti-cancer treatment-related toxicities (except alopecia) must be <= Grade

1 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. 0 at the time of enrollment

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Adequate baseline organ function as defined by: absolute neutrophil count (ANC) >=

1. 2 × 109/L; Hemoglobin >= 9 g/dL; Platelet count >= 100 x 109/L; prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) <= 1. 5 x upper limit of normal (ULN); Albumin >= 2. 5 g/dL; Total bilirubin <= 1. 5 x ULN; aspartate aminotransferase (AST) and alanine transaminase (ALT) <= 2. 0 x ULN; Creatinine <=1. 5 mg/mL; Left Ventricular Ejection fraction (LVEF) >= lower limit of normal (LLN) by ECHO Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and agree to use effective contraception, during the study, and for 30 days after the last dose of study treatment

- Men with a female partner of childbearing potential must have either had a prior

vasectomy or agree to use effective contraception for at least 2 weeks prior to the first dose of study treatment until 16 weeks after the last dose of study treatment to allow for clearance of any altered sperm

- Able to swallow and retain orally administered study treatment and does not have any

clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels Exclusion Criteria:

- Prior treatment with a BRAF inhibitors or a MEK inhibitor (including but not limited

to trametinib, AZD6244, and RDEA119) or ipilimumab or any other agent targeting a T-cell immunomodulatory pathway (including, but not limited to CTLA-4, PD-1, 4-1BB, OX40, GITR, CD27, and CD28)

- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity,

biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomization

- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C

- -----Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV

infection)

- A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency

- All known lesions were previously treated with surgery or stereotactic surgery

(whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery)

- Brain lesion(s), if still present, must be confirmed stable (i. e., no increase in

lesion size) for >= 6 weeks prior to randomization (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast,

- Asymptomatic with no corticosteroid requirements for >= 4 weeks prior to

randomization,

- No enzyme inducing anticonvulsants for >= 4 weeks prior to randomization

- A history or evidence of cardiovascular risk including any of the following LVEF <

LLN for the institution

- A corrected QT interval >=480 msec (e. g. Bazett's formula [QTcB])

- A history or evidence of current clinically significant uncontrolled arrhythmias

(exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible)

- A history (within 6 months prior to first dose of study treatment) of acute coronary

syndromes (including myocardial infarction or unstable angina), coronary angioplasty

- A history or evidence of current >=Class II congestive heart failure as defined by

the New York Heart Association (NYHA)

- Treatment refractory hypertension defined as systolic blood pressure >140 millimetres

of mercury (mmHg) and/or diastolic blood pressure >90 mmHg which cannot be controlled by antihypertensive therapy

- Patients with intra-cardiac defibrillators

- Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects

with grade 1 abnormalities [i. e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study

- A history or current evidence/risk of retinal vein occlusion (RVO) or Central serous

retinopathy (CSR) including

- Presence of predisposing factors to RVO or CSR (e. g., uncontrolled glaucoma or ocular

hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes), or

- Visible retinal pathology as assessed by ophthalmic examination that is considered a

risk factor for RVO or CSR such as evidence of new optic disc cupping; Evidence of new visual field defects on automated perimetry; Intraocular pressure >21 mmHg as measured by tonography

- History of any of the following diseases: inflammatory bowel disease or any other

autoimmune bowel disease; systemic lupus erythematosus; rheumatoid arthritis; or any autoimmune ocular diseases. Patients with active autoimmune disease or a history of autoimmune disease other than those mentioned above must be approved by the GSK medical monitor

- Active pneumonitis or interstitial lung disease

- Lactating female

- History of another malignancy (Exception: Subjects who have been disease-free for 3

years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible)

- Any serious and/or unstable pre-existing medical, psychiatric disorder or other

conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures

- Any prohibited medication

- Administration of an investigational study treatment within 28 days or 5 half-lives,

whichever is longer, preceding the first dose of study treatment(s) in this study

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs

chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO)

- Unwillingness or inability to follow the procedures outlined in the protocol

Locations and Contacts

Gomel Region Clinical Oncology Dispensary, Gomel, Belarus

N.N.Petrov Oncology Research Center, St.Petersburg 197758, Russian Federation

Cancer Centre, Dnepropetrovsk, Ukraine

Donetsk City Oncology Dispensary, Donetsk, Ukraine

Kharkiv Regional Clinical Oncology Center, Kharkiv, Ukraine

Additional Information

Starting date: September 2014
Last updated: July 24, 2015

Page last updated: August 20, 2015

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