Melanoma Clinical Trial
Official title:
A Phase III, Randomized, Double-blinded Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to Dabrafenib and Placebo as First-line Therapy in Subjects With Unresectable (Stage IIIC) or Metastatic (Stage IV) BRAF V600E/K Mutation-positive Cutaneous Melanoma
Verified date | February 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This was a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib and trametinib combination therapy to dabrafenib administered with a placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive were screened for eligibility. Subjects who had prior systemic anti-cancer treatment in the advanced or metastatic setting were not eligible although prior systemic treatment in the adjuvant setting was allowed. Subjects were stratified according to the baseline lactate dehydrogenase level and BRAF genotype.
Status | Completed |
Enrollment | 423 |
Est. completion date | February 28, 2019 |
Est. primary completion date | August 26, 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible. - The subject must have a radiologically measurable tumor - The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1). - Able to swallow and retain oral medication - Sexually active subjects must use acceptable methods of contraception during the course of the study - Adequate organ system function and blood counts Exclusion Criteria: - Prior treatment with a BRAF or a MEK inhibitor - Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.) - The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment - Current use of prohibited medication listed in the protocol - Left ventricular ejection fraction less than the lower limit of normal - Uncontrolled blood pressurl - History or current evidence of retinal vein occlusion or central serous retinopathy - Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks - The subject is pregnant or nursing |
Country | Name | City | State |
---|---|---|---|
Argentina | Novartis Investigative Site | Caba | Buenos Aires |
Argentina | Novartis Investigative Site | Capital Federal | Buenos Aires |
Argentina | Novartis Investigative Site | Ciudad Autonoma de Buenos Aires | Buenos Aires |
Australia | Novartis Investigative Site | Adelaide | South Australia |
Australia | Novartis Investigative Site | Heidelberg | Victoria |
Australia | Novartis Investigative Site | Nedlands | Western Australia |
Australia | Novartis Investigative Site | North Sydney | New South Wales |
Australia | Novartis Investigative Site | Westmead | New South Wales |
Australia | Novartis Investigative Site | Woolloongabba | Queensland |
Canada | Novartis Investigative Site | Edmonton | Alberta |
Canada | Novartis Investigative Site | Hamilton | Ontario |
Canada | Novartis Investigative Site | London | Ontario |
Canada | Novartis Investigative Site | Montreal | Quebec |
Canada | Novartis Investigative Site | Montreal | Quebec |
Canada | Novartis Investigative Site | Toronto | Ontario |
France | Novartis Investigative Site | Bordeaux | |
France | Novartis Investigative Site | Boulogne-Billancourt | |
France | Novartis Investigative Site | Lyon Cedex 08 | |
France | Novartis Investigative Site | Marseille cedex 5 | |
France | Novartis Investigative Site | Paris | |
France | Novartis Investigative Site | Paris | |
France | Novartis Investigative Site | Paris Cedex 10 | |
France | Novartis Investigative Site | Toulouse Cedex | |
France | Novartis Investigative Site | Vandoeuvre les Nancy | |
Germany | Novartis Investigative Site | Augsburg | Bayern |
Germany | Novartis Investigative Site | Berlin | |
Germany | Novartis Investigative Site | Bonn | Nordrhein-Westfalen |
Germany | Novartis Investigative Site | Buxtehude | Niedersachsen |
Germany | Novartis Investigative Site | Darmstadt | Hessen |
Germany | Novartis Investigative Site | Dresden | Sachsen |
Germany | Novartis Investigative Site | Erfurt | Thueringen |
Germany | Novartis Investigative Site | Erlangen | Bayern |
Germany | Novartis Investigative Site | Essen | Nordrhein-Westfalen |
Germany | Novartis Investigative Site | Gera | Thueringen |
Germany | Novartis Investigative Site | Hannover | Niedersachsen |
Germany | Novartis Investigative Site | Heidelberg | Baden-Wuerttemberg |
Germany | Novartis Investigative Site | Heilbronn | Baden-Wuerttemberg |
Germany | Novartis Investigative Site | Homburg | Saarland |
Germany | Novartis Investigative Site | Jena | Thueringen |
Germany | Novartis Investigative Site | Kiel | Schleswig-Holstein |
Germany | Novartis Investigative Site | Koeln | Nordrhein-Westfalen |
Germany | Novartis Investigative Site | Leipzig | Sachsen |
Germany | Novartis Investigative Site | Luebeck | Schleswig-Holstein |
Germany | Novartis Investigative Site | Magdeburg | Sachsen-Anhalt |
Germany | Novartis Investigative Site | Mainz | Rheinland-Pfalz |
Germany | Novartis Investigative Site | Mannheim | Baden-Wuerttemberg |
Germany | Novartis Investigative Site | Marburg | Hessen |
Germany | Novartis Investigative Site | Muenchen | Bayern |
Germany | Novartis Investigative Site | Muenchen | Bayern |
Germany | Novartis Investigative Site | Muenchen | Bayern |
Germany | Novartis Investigative Site | Nuernberg | Bayern |
Germany | Novartis Investigative Site | Regensburg | Bayern |
Germany | Novartis Investigative Site | Tuebingen | Baden-Wuerttemberg |
Germany | Novartis Investigative Site | Ulm | Baden-Wuerttemberg |
Germany | Novartis Investigative Site | Wuerzburg | Bayern |
Greece | Novartis Investigative Site | Athens | |
Greece | Novartis Investigative Site | N. Faliro | |
Greece | Novartis Investigative Site | Thessaloniki | |
Italy | Novartis Investigative Site | Bergamo | Lombardia |
Italy | Novartis Investigative Site | Candiolo (TO) | Piemonte |
Italy | Novartis Investigative Site | Genova | Liguria |
Italy | Novartis Investigative Site | Milano | Lombardia |
Italy | Novartis Investigative Site | Milano | Lombardia |
Italy | Novartis Investigative Site | Padova | Veneto |
Italy | Novartis Investigative Site | Roma | Lazio |
Italy | Novartis Investigative Site | Roma | Lazio |
Netherlands | Novartis Investigative Site | Amsterdam | |
Netherlands | Novartis Investigative Site | Amsterdam | |
Netherlands | Novartis Investigative Site | Zwolle | |
Russian Federation | Novartis Investigative Site | Kazan | |
Russian Federation | Novartis Investigative Site | Moscow | |
Russian Federation | Novartis Investigative Site | St. Petersburg | |
Russian Federation | Novartis Investigative Site | Stavropol | |
Spain | Novartis Investigative Site | Barcelona | |
Spain | Novartis Investigative Site | Barcelona | |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Pamplona | |
Spain | Novartis Investigative Site | Valencia | |
Sweden | Novartis Investigative Site | Goteborg | |
Sweden | Novartis Investigative Site | Lund | |
Sweden | Novartis Investigative Site | Stockholm | |
Sweden | Novartis Investigative Site | Uppsala | |
Ukraine | Novartis Investigative Site | Dnipropetrovsk | |
Ukraine | Novartis Investigative Site | Dnipropetrovsk | |
Ukraine | Novartis Investigative Site | Donetsk | |
Ukraine | Novartis Investigative Site | Khmelnytskyi | |
Ukraine | Novartis Investigative Site | Kyiv | |
Ukraine | Novartis Investigative Site | Lviv | |
Ukraine | Novartis Investigative Site | Sumy | |
United Kingdom | Novartis Investigative Site | Aberdeen | |
United Kingdom | Novartis Investigative Site | Bebington | |
United Kingdom | Novartis Investigative Site | Edgbaston, Birmingham | |
United Kingdom | Novartis Investigative Site | Leeds | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | Newcastle upon Tyne | |
United Kingdom | Novartis Investigative Site | Northwood | Middlesex |
United Kingdom | Novartis Investigative Site | Nottingham | |
United Kingdom | Novartis Investigative Site | Oxford | |
United Kingdom | Novartis Investigative Site | Preston | |
United Kingdom | Novartis Investigative Site | Sutton | Surrey |
United States | Novartis Investigative Site | Boston | Massachusetts |
United States | Novartis Investigative Site | Boston | Massachusetts |
United States | Novartis Investigative Site | Chattanooga | Tennessee |
United States | Novartis Investigative Site | Cincinnati | Ohio |
United States | Novartis Investigative Site | Columbia | South Carolina |
United States | Novartis Investigative Site | Fort Myers | Florida |
United States | Novartis Investigative Site | Fort Worth | Texas |
United States | Novartis Investigative Site | Indianapolis | Indiana |
United States | Novartis Investigative Site | Los Angeles | California |
United States | Novartis Investigative Site | Nashville | Tennessee |
United States | Novartis Investigative Site | New York | New York |
United States | Novartis Investigative Site | Peoria | Illinois |
United States | Novartis Investigative Site | Philadelphia | Pennsylvania |
United States | Novartis Investigative Site | Richmond | Virginia |
United States | Novartis Investigative Site | Saint Petersburg | Florida |
United States | Novartis Investigative Site | Scottsdale | Arizona |
United States | Novartis Investigative Site | Tampa | Florida |
United States | Novartis Investigative Site | Tucson | Arizona |
United States | Novartis Investigative Site | West Palm Beach | Florida |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Argentina, Australia, Canada, France, Germany, Greece, Italy, Netherlands, Russian Federation, Spain, Sweden, Ukraine, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Progression-Free Survival (PFS) as Assessed by the Investigator | PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm. The appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation, was also included as PD. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not have documented progression or death, PFS was censored at the date of the last adequate assessment. | From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years) | |
Secondary | Overall Survival (OS) | OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact. | From the date of randomization until date of death due to any cause (up to approximately 6 years) | |
Secondary | Objective Response Rate (ORR) as Assessed by the Investigator | ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of =10mm). Only descriptive analysis performed. | From randomization until the first documented complete response or partial response (up to approximately 6 years) | |
Secondary | Duration of Response (DoR) | Duration of response is defined as the time from the first documented complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of =10mm) until disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5mm or the appearance of one or more new lesions, or the worsening of non target lesions significant enough to require study treatment discontinuation. PD was based on the radiological evidence by investigator. Only descriptive analysis performed. | From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years) | |
Secondary | Trametinib Pharmacokinetic Concentrations | Blood samples were collected for Pharmacokinetic (PK) analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Only descriptive analysis performed. | Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose) | |
Secondary | Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations | Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of Dabrafenib (GSK2118436) and its metabolites (Hydroxy-Dabrafenib (GSK2285403), Carboxy-Dabrafenib (GSK2298683), and Desmethyl-Dabrafenib (GSK2167542)) were determined using the currently approved analytical methodology. Only descriptive analysis performed. | Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose) | |
Secondary | Number of Participants With Adverse Events and Serious Adverse Events | Analysis of absolute and relative frequencies for Adverse Event (AE) and Serious Adverse Event (SAE) by primary System Organ Class (SOC) to characterize the safety of dabrafenib and trametinib combination therapy through the monitoring of relevant clinical and laboratory safety parameters. In addition, new malignancies and AEs possibly related to study treatment were collected even if they occurred more than 30 days post-treatment. Only descriptive analysis performed. | From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (up to approximately 6 years). |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Completed |
NCT03979872 -
Risk Information and Skin-cancer Education for Undergraduate Prevention
|
N/A | |
Recruiting |
NCT04986748 -
Using QPOP to Predict Treatment for Sarcomas and Melanomas
|
||
Enrolling by invitation |
NCT00068003 -
Harvesting Cells for Experimental Cancer Treatments
|
||
Recruiting |
NCT05707286 -
Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
|
||
Active, not recruiting |
NCT05470283 -
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
|
Phase 1 | |
Recruiting |
NCT05077137 -
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
|
Phase 1 | |
Active, not recruiting |
NCT02721459 -
XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma
|
Phase 1 | |
Completed |
NCT00341939 -
Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
|
||
Recruiting |
NCT05839912 -
Excision of Lymph Node Trial (EXCILYNT) (Mel69)
|
N/A | |
Recruiting |
NCT04971499 -
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
|
Phase 1/Phase 2 | |
Recruiting |
NCT05263453 -
HL-085+Vemurafenib to Treat Advanced Melanoma Patients With BRAF V600E/K Mutation
|
Phase 2 | |
Active, not recruiting |
NCT05060432 -
Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT06413680 -
A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies
|
Phase 1/Phase 2 | |
Completed |
NCT03348891 -
TNF in Melanoma Patients Treated With Immunotherapy
|
N/A | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT03171064 -
Exercise as a Supportive Measure for Patients Undergoing Checkpoint-inhibitor Treatment
|
Phase 2 | |
Not yet recruiting |
NCT05539118 -
Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma
|
Phase 1/Phase 2 | |
Recruiting |
NCT05171374 -
pRospective Evaluation of Clinical Outcomes in Patients With metAsTatIс melanOma Treated With dabrafeNib and trAmetinib in reaL practicE
|
||
Withdrawn |
NCT02854488 -
Yervoy Pregnancy Surveillance Study
|