Health Condition 1: E078- Other specified disorders of thyroid Health Condition 2: L99- Other disorders of skin and subcutaneous tissue in diseases classified elsewhere Health Condition 3: J984- Other disorders of lung
Conditions
Interventions
Intervention1: Dabrafenib Mesylate 150 mg capsules.: Dabrafenib Mesylate capsules 150 mg will be administered twice daily with 12 hours interval between two dosing along with Trametinib 2 mg with 240
Sponsors
Rising Pharma Holdings, Inc.,
Jeevan Scientific Technology Limited
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria: Patient must meet all of the following inclusion criteria to be eligible for enrollment into the study. 1.Men or woman aged equal or more than 18 years. 2.Histologically confirmed diagnosis of adult patients with a BRAFV600E or V600K mutations detection test. 3.Participants who are already receiving a stable dose of Dabrafenib Mesylate capsules will be included in the study. 4.Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. 5.Karnofsky performance status (KPS) equal or more than 70 Percentage. 6.Women of childbearing potential (WOCBP) and men with reproductive potential must agree to use effective contraception during the study and at least two weeks after the last dose. WOCBP must have a negative serum pregnancy test within 14 days prior to randomization. 7.Eastern Cooperative Oncology Group (ECOG) Performance Status equal or less than 1. 8.Life expectancy of greater than at least 3-6 months. 9.Left ventricular ejection fraction same or more than institutional lower limit of normal (LLN) by echocardiogram (ECHO) 10.Patients must not receive any other investigational agents while on study or within four weeks prior to registration. 11.Patients must not have evidence of interstitial lung disease or pneumonitis. 12.Ability to understand and the willingness to sign a written informed consent document. 13.Adequate function of major organs, meeting the following criteria: Hematologic parameters: WBC equal or more than 4.0 10^9per litre ANC equal or more than 1.5 10^9per litre PLT equal or more than 100 10^9per litre Hb equal or more than 90 gram per litre. Biochemical parameters: Serum albumin equal or more than 3.0 gram/ desi litre (30 gram per litre) TBIL equal or less 1.5 ULN ALT and AST equal or less than 2.5 ULN BUN and creatinine equal or less than 1.5 ULN or estimated creatinine clearance equal or more than 60 milli litre /minute (by Cockcroft-Gault formula). Coagulation: INR or PT equal or less than 1.5 ULN for subjects on anticoagulation therapy, PT must be within the therapeutic range defined by the medication.
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Patient presenting with any of the following will not be included in the study and the reason for exclusion from the study will be documented: 1.Patients with colorectal cancer and wild type BRAF solid tumors will not be enrolled in the study. 2.Any prior use of BRAF inhibitors (BRAFi) MEK inhibitors (MEKi) or ipilimumab in the advanced or metastatic setting. 3.Exclude patients who require dosage modification or with expected changes in concomitant medications (e.g. trametinib) that may potentially affect the pharmacokinetics of Dabrafenib Mesylate during the study. 4.Patient with ocular melanoma are not eligible. 5.Any major surgery extensive radiotherapy chemotherapy with delayed toxicity biologic therapy or immunotherapy within the last 21 days. Chemotherapy given daily or weekly without the potential for delayed toxicity within the last 14 days. 6.Current use of any prohibited medication. 7. Participants taking corticosteroids (equal or more than 10 mg of prednisone or equivalent). Exceptions may be discussed with the overall PI on a case by case basis. 8. Participants with a personal or family history of long QT syndrome. 9. Historical or current evidence of significant hematologic hepatic neurologic psychiatric renal or other diseases that in the opinion of the investigator would put the Patient at risk through study participation or would affect the study analyses if the disease exacerbates during the study. 10. History of another malignancy with the exception of patients who have been disease-free for 3 years or patients with a history of completely resected non-melanoma skin cancer. 11.Any serious and or unstable pre-existing medical psychiatric disorder or other conditions that could interfere with patient safety obtaining informed consent or complying with study procedures. 12.Known Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. 13.History or evidence of cardiovascular risk including any of the following: History or evidence of current clinically significant uncontrolled arrhythmia with the exception of atrial fibrillation that will be controlled for more than 30 days prior to randomization. History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina) coronary angioplasty or stenting. History or evidence of current equal or more than Class II congestive heart failure as defined by New York Heart Association (NYHA). Significant uncontrolled or active cardiovascular disease specifically including but not restricted to: History of clinically significant (as determined by the treating physician) atrial arrhythmia; or any ventricular arrhythmia History of congenital long QT syndrome. Abnormal QTc (equal or more than 450 msec in males and equal or more than 470 msec in females) Ejection fraction equal or less than 50 percentage as assessed by echocardiogram. History of arterial thrombotic disease specifically including but not restricted to: Myocardial infarction or unstable angina cerebrovascular event (CVA) or transient ischemic attack (TIA) Peripheral vascular disease or claudication. Uncontrolled hypertension (Diastolic blood pressure more than 100 mmHg Systolic blood pressure more than 150 mmHg). 14.History of venous thromboembolism (e.g. deep venous thrombosis or pulmonary embolism) within 6 months of study entry. Note: Participants enrolled after this window must be on app
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration Time Curve from time 0 to the end of the dosing interval at Steady State Maximum (peak) plasma drug concentration at Steady StateTimepoint: Period I Day 12 Day 13 Day 14 Day 15 Day 16 Period II Day 27 Day 28 Day 29 Day 30 Day 31 | — |
Secondary
| Measure | Time frame |
|---|---|
| Minimum (trough) plasma drug concentration at Steady State Plasma drug concentration at the end of the dosing interval at Steady State Average plasma drug concentration over the dosing interval at Steady State Time to reach maximum plasma drug concentration at Steady State Terminal elimination half-life at Steady State Peak-to-trough fluctuation in plasma drug concentration at Steady State Peak-to-trough fluctuation in plasma drug concentration at Steady StateTimepoint: Period I Day 12 Day 13 Day 14 Day 15 Day 16 Period II Day 27 Day 28 Day 29 Day 30 Day 31 | — |
Countries
India
Contacts
Public ContactDr Suman Avula
Jeevan Scientific Technology Limited
Outcome results
None listed