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BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced (Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will be allowed to crossover to an optional extension arm of the study to receive GSK2118436.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2118436 | Experimental | Subjects in this arm will receive GSK2118436 150 mg twice daily. |
|
| Dacarbazine (DTIC) | Active Comparator | Subjects will receive intravenous dacarbazine (DTIC) 1000 mg/m2 every 3 weeks |
|
| Crossover | Experimental | Subjects who initially receive DTIC will be allowed to receive GSK2118436 after initial progression. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2118436 | Drug | 150 mg twice daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) as Assessed by the Investigator | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not progress or die, PFS was censored at the date of last contact. Data are presented as median and 96% confidence interval. | Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) |
| Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by an independent radiologist 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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact. | Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. | Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Birmingham | Alabama | 35243 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22735384 | Background | Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martin-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012 Jul 28;380(9839):358-65. doi: 10.1016/S0140-6736(12)60868-X. Epub 2012 Jun 25. | |
| 31864178 |
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The study has 2 phases: Randomized and Crossover Phase. In Randomized Phase, a total of 250 par. were randomized in 3:1 to receive either oral dabrafenib 150 mg twice daily (BID) or intravenous DTIC 1000 milligram/meter square. Par. in DTIC arm with disease progression were considered for crossover to dabrafenib arm in Crossover Phase
This was a Phase III randomized, open-label study to compare GSK2118436 to Dacarbazine (DTIC) in previously untreated participants (par.) with BRAF mutation positive advanced (Stage III) or metastatic (Stage IV) melanoma. This study was conducted at 70 centers in 12 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | GSK2118436 150 mg BID | Participants (par.) were randomly assigned to receive oral GSK2118436 150 milligrams (mg) twice a day (BID). Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until disease progression (DP), death, the occurrence of an unacceptable adverse event (AE), or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomized Phase (RP) |
|
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| Dacarbazine (DTIC) |
| Drug |
Intravenous (IV), 1000 mg/m2 every 3 weeks until initial progression |
|
| Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Randomized Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks) |
| Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an independent radiologist per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks) |
| Duration of Response as Assessed by the Investigator: Randomized Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks) |
| Duration of Response as Assessed by an Independent Radiologist: Randomized Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. NA indicates that data is not available. | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months) |
| Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase | PFS2 is defined as the time from the first dose of GSK2118436, in participants randomized to DTIC who crossed over to GSK2118436 after initial progression, to the earliest date of radiographic or photographic disease progression or death due to any cause. Disease progression 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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact. | Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months) |
| Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Crossover Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months) |
| Duration of Response as Assessed by the Investigator: Crossover Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months) |
| Number of Participants With Non-melanoma Skin Lesions: Randomized Phase | Dermatological examinations were performed by the investigator, or at the discretion of the investigator, referred to a dermatologist. The number of participants with non-melanoma skin lessions was assessed from the time of Screening until study completion or discontinuation from the study for any reason. | From Screening until study completion or discontinuation from the study (up to 9.9 months) |
| Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay | Analytical and clinical validation of the companion diagnostic (cDx) assay was performed to determine the extent of agreement between the bioMerieux cDx assay (THxID BRAF Assay) and the Clinical Trial Assay (CTA) to detect BRAF mutations to determine participant eligibility into the study. Skin tissue samples collected at the Screening visit were used for this analysis. Multiple specimen per participant were analyzed. | Screening |
| Mobile |
| Alabama |
| 36608 |
| United States |
| GSK Investigational Site | La Jolla | California | 92093 | United States |
| GSK Investigational Site | Los Angeles | California | 90095 | United States |
| GSK Investigational Site | San Francisco | California | 94115 | United States |
| GSK Investigational Site | Vallejo | California | 94589 | United States |
| GSK Investigational Site | Orlando | Florida | 32806 | United States |
| GSK Investigational Site | Indianapolis | Indiana | 46202 | United States |
| GSK Investigational Site | Ann Arbor | Michigan | 48109 | United States |
| GSK Investigational Site | Lebanon | New Hampshire | 03756 | United States |
| GSK Investigational Site | New York | New York | 10065 | United States |
| GSK Investigational Site | Westmead | New South Wales | 2145 | Australia |
| GSK Investigational Site | Southport | Queensland | 4215 | Australia |
| GSK Investigational Site | Adelaide | South Australia | 5000 | Australia |
| GSK Investigational Site | Nedlands | Western Australia | 6009 | Australia |
| GSK Investigational Site | Edmonton | Alberta | T6G 1Z2 | Canada |
| GSK Investigational Site | Kelowna | British Columbia | V1Y 5L3 | Canada |
| GSK Investigational Site | Toronto | Ontario | M4N 3M5 | Canada |
| GSK Investigational Site | Toronto | Ontario | M5G 2M9 | Canada |
| GSK Investigational Site | Montreal | Quebec | H3T 1E2 | Canada |
| GSK Investigational Site | Bordeaux | 33075 | France |
| GSK Investigational Site | Lille | 59037 | France |
| GSK Investigational Site | Marseille | 13385 | France |
| GSK Investigational Site | Nice | 06202 | France |
| GSK Investigational Site | Paris | 75006 | France |
| GSK Investigational Site | Paris | 75877 | France |
| GSK Investigational Site | Reims | 51092 | France |
| GSK Investigational Site | Villejuif | 94805 | France |
| GSK Investigational Site | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| GSK Investigational Site | Ulm | Baden-Wurttemberg | 89081 | Germany |
| GSK Investigational Site | Erlangen | Bavaria | 91054 | Germany |
| GSK Investigational Site | Nuremberg | Bavaria | 90419 | Germany |
| GSK Investigational Site | Regensburg | Bavaria | 93053 | Germany |
| GSK Investigational Site | Kassel | Hesse | 34125 | Germany |
| GSK Investigational Site | Wiesbaden | Hesse | 65191 | Germany |
| GSK Investigational Site | Hanover | Lower Saxony | 30449 | Germany |
| GSK Investigational Site | Bonn | North Rhine-Westphalia | 53127 | Germany |
| GSK Investigational Site | Cologne | North Rhine-Westphalia | 50937 | Germany |
| GSK Investigational Site | Essen | North Rhine-Westphalia | 45122 | Germany |
| GSK Investigational Site | Münster | North Rhine-Westphalia | 48149 | Germany |
| GSK Investigational Site | Koblenz | Rhineland-Palatinate | 56068 | Germany |
| GSK Investigational Site | Ludwigshafen am Rhein | Rhineland-Palatinate | 67063 | Germany |
| GSK Investigational Site | Mainz | Rhineland-Palatinate | 55131 | Germany |
| GSK Investigational Site | Homburg | Saarland | 66421 | Germany |
| GSK Investigational Site | Magdeburg | Saxony-Anhalt | 39120 | Germany |
| GSK Investigational Site | Kiel | Schleswig-Holstein | 24105 | Germany |
| GSK Investigational Site | Erfurt | Thuringia | 99089 | Germany |
| GSK Investigational Site | Gera | Thuringia | 07548 | Germany |
| GSK Investigational Site | Jena | Thuringia | 07740 | Germany |
| GSK Investigational Site | Budapest | H-1122 | Hungary |
| GSK Investigational Site | Debrecen | 4032 | Hungary |
| GSK Investigational Site | Győr | H-9024 | Hungary |
| GSK Investigational Site | Miskolc | 3526 | Hungary |
| GSK Investigational Site | Pécs | 7624 | Hungary |
| GSK Investigational Site | Cork | Ireland |
| GSK Investigational Site | Dublin | 4 | Ireland |
| GSK Investigational Site | Dublin | 7 | Ireland |
| GSK Investigational Site | Dublin | 8 | Ireland |
| GSK Investigational Site | Dublin | 9 | Ireland |
| GSK Investigational Site | Galway | Co Galway | Ireland |
| GSK Investigational Site | Modena | Emilia-Romagna | 41100 | Italy |
| GSK Investigational Site | Udine | Friuli Venezia Giulia | 33100 | Italy |
| GSK Investigational Site | Rome | Lazio | 00144 | Italy |
| GSK Investigational Site | Rome | Lazio | 00167 | Italy |
| GSK Investigational Site | Genoa | Liguria | 16132 | Italy |
| GSK Investigational Site | Rozzano (MI) | Lombardy | 20089 | Italy |
| GSK Investigational Site | Siena | Tuscany | 53100 | Italy |
| GSK Investigational Site | Terni | Umbria | 05100 | Italy |
| GSK Investigational Site | Padova | Veneto | 35128 | Italy |
| GSK Investigational Site | Amsterdam | 1066 CX | Netherlands |
| GSK Investigational Site | Brzozów | 36-200 | Poland |
| GSK Investigational Site | Konin | 62-500 | Poland |
| GSK Investigational Site | Krakow | 31-115 | Poland |
| GSK Investigational Site | SÅ‚upsk | 76-200 | Poland |
| GSK Investigational Site | Warsaw | 02-781 | Poland |
| GSK Investigational Site | Kazan' | 420029 | Russia |
| GSK Investigational Site | Moscow | 115478 | Russia |
| GSK Investigational Site | Ryazan | 390011 | Russia |
| GSK Investigational Site | Saint Petersburg | 191104 | Russia |
| GSK Investigational Site | Saint Petersburg | 197758 | Russia |
| GSK Investigational Site | Saint Petersburg | 198255 | Russia |
| GSK Investigational Site | Stavropol | 355047 | Russia |
| GSK Investigational Site | Badalona | 08916 | Spain |
| GSK Investigational Site | Barcelona | 08035 | Spain |
| GSK Investigational Site | Barcelona | 08036 | Spain |
| GSK Investigational Site | Hospitalet de Llobregat, Barcelona | 08907 | Spain |
| GSK Investigational Site | Madrid | 28007 | Spain |
| GSK Investigational Site | Madrid | 28033 | Spain |
| GSK Investigational Site | Madrid | 28034 | Spain |
| GSK Investigational Site | Madrid | 28040 | Spain |
| GSK Investigational Site | Madrid | 28041 | Spain |
| GSK Investigational Site | Madrid | 28050 | Spain |
| GSK Investigational Site | Pamplona | 31008 | Spain |
| GSK Investigational Site | Seville | 41013 | Spain |
| Derived |
| Hauschild A, Ascierto PA, Schadendorf D, Grob JJ, Ribas A, Kiecker F, Dutriaux C, Demidov LV, Lebbe C, Rutkowski P, Blank CU, Gutzmer R, Millward M, Kefford R, Haas T, D'Amelio A Jr, Gasal E, Mookerjee B, Chapman PB. Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib monotherapy: Analysis from phase 2 and 3 clinical trials. Eur J Cancer. 2020 Jan;125:114-120. doi: 10.1016/j.ejca.2019.10.033. |
| 26446943 | Derived | Santiago-Walker A, Gagnon R, Mazumdar J, Casey M, Long GV, Schadendorf D, Flaherty K, Kefford R, Hauschild A, Hwu P, Haney P, O'Hagan A, Carver J, Goodman V, Legos J, Martin AM. Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials. Clin Cancer Res. 2016 Feb 1;22(3):567-74. doi: 10.1158/1078-0432.CCR-15-0321. Epub 2015 Oct 7. |
| 26040620 | Derived | Latimer NR, Abrams KR, Amonkar MM, Stapelkamp C, Swann RS. Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine. Oncologist. 2015 Jul;20(7):798-805. doi: 10.1634/theoncologist.2014-0429. Epub 2015 Jun 3. |
| 24769640 | Derived | Grob JJ, Amonkar MM, Martin-Algarra S, Demidov LV, Goodman V, Grotzinger K, Haney P, Kampgen E, Karaszewska B, Mauch C, Miller WH Jr, Millward M, Mirakhur B, Rutkowski P, Chiarion-Sileni V, Swann S, Hauschild A. Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: quality-of-life analyses of the BREAK-3 study comparing dabrafenib with dacarbazine. Ann Oncol. 2014 Jul;25(7):1428-1436. doi: 10.1093/annonc/mdu154. Epub 2014 Apr 25. |
| 24408395 | Derived | Ouellet D, Gibiansky E, Leonowens C, O'Hagan A, Haney P, Switzky J, Goodman VL. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014 Jun;54(6):696-706. doi: 10.1002/jcph.263. Epub 2014 Jan 17. |
| FG001 | DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase | In the RP, par. received intravenous (IV) Dacarbazine (DTIC) 1000 mg per meters squared (mg/m^2) every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy. |
| COMPLETED |
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| NOT COMPLETED |
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| Crossover Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | GSK2118436 150 mg BID | Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. |
| BG001 | DTIC 1000 mg/m^2 in RP; GSK2118436 in Crossover Phase | In the RP, par. received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Par. continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Par. who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Par. who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover par. continued on GSK2118436 until further DP was noted. After DP on GSK2118436, par. were followed for response, progression, survival, and further anti-cancer therapy. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression-free Survival (PFS) as Assessed by the Investigator | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not progress or die, PFS was censored at the date of last contact. Data are presented as median and 96% confidence interval. | Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not treatment was administered | Posted | Median | 95% Confidence Interval | Months | Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) |
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| Primary | Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase | PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by an independent radiologist 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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact. | ITT Population | Posted | Median | 95% Confidence Interval | Months | Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months) |
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| Secondary | Overall Survival | Overall survival is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. | ITT Population | Posted | Median | 95% Confidence Interval | Months | Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months) |
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| Secondary | Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Randomized Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | ITT Population | Posted | Number | participants | From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an independent radiologist per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | ITT Population | Posted | Number | participants | From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response as Assessed by the Investigator: Randomized Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. | ITT Population. Only participants with a confirmed CR or PR were assessed for duration of response. | Posted | Median | 95% Confidence Interval | Months | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response as Assessed by an Independent Radiologist: Randomized Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. NA indicates that data is not available. | ITT Population. Only participants with a confirmed CR or PR were assessed for duration of response. | Posted | Median | 95% Confidence Interval | Months | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase | PFS2 is defined as the time from the first dose of GSK2118436, in participants randomized to DTIC who crossed over to GSK2118436 after initial progression, to the earliest date of radiographic or photographic disease progression or death due to any cause. Disease progression 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 (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact. | Crossover Treatment Population: the subset of participants who were randomized to the DTIC arm, and who elected at the point of disease progression to receive GSK2118436. Only participants who received at least one dose of GSK2118436 were included in the Crossover Treatment Population. | Posted | Median | 95% Confidence Interval | Months | Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Crossover Phase | A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR. | Crossover Treatment Population. At the time data were analyzed for overall response, only 37 participants had crossed over from DTIC treatment to GSK25118436 treatment. | Posted | Number | participants | From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response as Assessed by the Investigator: Crossover Phase | Duration of response for participants with either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or 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 [e.g., percent change from Baseline]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of 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, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. | Crossover Population. Only participants with a confirmed CR or PR were assessed for duration of response. | Posted | Median | 95% Confidence Interval | Months | Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Non-melanoma Skin Lesions: Randomized Phase | Dermatological examinations were performed by the investigator, or at the discretion of the investigator, referred to a dermatologist. The number of participants with non-melanoma skin lessions was assessed from the time of Screening until study completion or discontinuation from the study for any reason. | Safety Population: all randomized participants who received at least one dose of study drug, based on the actual treatment received, if this differed from that to which the participant was randomized | Posted | Number | participants | From Screening until study completion or discontinuation from the study (up to 9.9 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay | Analytical and clinical validation of the companion diagnostic (cDx) assay was performed to determine the extent of agreement between the bioMerieux cDx assay (THxID BRAF Assay) and the Clinical Trial Assay (CTA) to detect BRAF mutations to determine participant eligibility into the study. Skin tissue samples collected at the Screening visit were used for this analysis. Multiple specimen per participant were analyzed. | V600E positive participants screened for BREAK-3 study | Posted | Number | 95% Confidence Interval | Percent agreement | Screening |
|
|
Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to the end of the study. The total duration of the study including a long-term follow-up phase was up to 5 years.
SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study drug, based on the actual treatment received, if this differed from that to which the participant was randomized.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK2118436 150 mg BID | Participants were randomly assigned to receive oral GSK2118436 150 mg BID. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. Participants who experienced investigator-reported DP but were benefitting from study treatment were permitted to continue GSK2118436 treatment upon approval of the GlaxoSmithKline Medical Monitor. | 5 | 187 | 64 | 187 | 181 | 187 |
| EG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. | 0 | 59 | 14 | 59 | 51 | 59 |
| EG002 | GSK25118436 in the Crossover Phase | Participants who received DTIC in the RP and experienced DP had the option, at the discretion of the Investigator, of receiving GSK2118436 150 mg BID in the Crossover Phase. Participants who permanently discontinued DTIC treatment due to an AE, withdrawal of consent, or for any reason other than DP were not eligible for crossover to GSK2118436. Crossover participants continued on GSK2118436 until further DP was noted. After DP on GSK2118436, participants were followed for response, progression, survival, and further anti-cancer therapy. | 1 | 37 | 9 | 37 | 37 | 37 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | 19.0 | Systematic Assessment |
| |
| Cataract | Eye disorders | 19.0 | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Pancreatic necrosis | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Chills | General disorders | 19.0 | Systematic Assessment |
| |
| Euthanasia | General disorders | 19.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | 19.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | 19.0 | Systematic Assessment |
| |
| Pain | General disorders | 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 19.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | 19.0 | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | 19.0 | Systematic Assessment |
| |
| Abdominal infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Hepatitis E | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Perineal abscess | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Pleural infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | 19.0 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | 19.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | 19.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | 19.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | 19.0 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | 19.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | 19.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Acoustic neuroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Adenocarcinoma of the cervix | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Focal nodular hyperplasia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Lip squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Malignant melanoma in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Malignant melanoma stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Papillary thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Soft tissue sarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Parkinsonism | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 19.0 | Systematic Assessment |
| |
| Psychotic disorder | Psychiatric disorders | 19.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | 19.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | 19.0 | Systematic Assessment |
| |
| Urinary bladder polyp | Renal and urinary disorders | 19.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | 19.0 | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | 19.0 | Systematic Assessment |
| |
| Macular hole | Eye disorders | 19.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Fibrous histiocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | 19.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | 19.0 | Systematic Assessment |
| |
| Chills | General disorders | 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | 19.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | 19.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | 19.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | 19.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | 19.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | 19.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | 19.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | 19.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 19.0 | Systematic Assessment |
| |
| Acrochordon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | 19.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Hair texture abnormal | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Palmoplantar keratoderma | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 19.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | 19.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | 19.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | 19.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | 19.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | 19.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | 19.0 | Systematic Assessment |
| |
| Dysplastic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Fibroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Fibrous histiocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19.0 | Systematic Assessment |
| |
| Hyperaesthesia | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | 19.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 19.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | 19.0 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | 19.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | 19.0 | Systematic Assessment |
| |
| INFLUENZA | Infections and infestations | 19.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C561627 | dabrafenib |
| D003606 | Dacarbazine |
| ID | Term |
|---|---|
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Progressive Disease |
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| Study Terminated By Sponsor |
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| Withdrawal by Subject |
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| Male |
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| Missing |
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| OG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. |
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| OG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. |
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| OG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. |
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| OG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. |
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| OG001 | DTIC 1000 mg/m^2 in RP | In the RP, participants received IV DTIC 1000 mg/m^2 every 3 weeks. Dose reductions were permitted based on the severity of the hematological toxicity. Stopping recommendations for study treatment were also provided for cases of reoccurring skin toxicity, cardiovascular complication or abnormalities, and liver abnormalities. Participants continued on treatment until DP, death, the occurrence of an unacceptable AE, or withdrawal from the study. |
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