TriangleNCT01227889 · CITED IN SOURCE DOCUMENTS
A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2017-10-04
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS) as Assessed by the Investigator
Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase
Overall Survival
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
Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase
Duration of Response as Assessed by the Investigator: Randomized Phase
Duration of Response as Assessed by an Independent Radiologist: Randomized Phase
Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase
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
Duration of Response as Assessed by the Investigator: Crossover Phase
Number of Participants With Non-melanoma Skin Lesions: Randomized Phase
Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Adults at least 18 years of age * Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E) * Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed. * Has measurable disease according to RECIST 1.1 criteria. * Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment. * Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication. * Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication. * Must have adequate organ function. * Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. Exclusion Criteria: * Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery). * Evidence of active central nervous system (CNS) disease. * Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor. * A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * History of Human Immunodeficiency Virus (HIV) infection. * Certain cardiac abnormalities
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Subjects in this arm will receive GSK2118436 150 mg twice daily.
- intervention Names
- Drug: GSK2118436
- label
- GSK2118436
- type
- EXPERIMENTAL
- description
- Subjects will receive intravenous dacarbazine (DTIC) 1000 mg/m2 every 3 weeks
- intervention Names
- Drug: Dacarbazine (DTIC)
- label
- Dacarbazine (DTIC)
- type
- ACTIVE_COMPARATOR
- description
- Subjects who initially receive DTIC will be allowed to receive GSK2118436 after initial progression.
- intervention Names
- Drug: GSK2118436
- label
- Crossover
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Crossover
- GSK2118436
- description
- 150 mg twice daily
- name
- GSK2118436
- type
- DRUG
- arm Group Labels
- Dacarbazine (DTIC)
- description
- Intravenous (IV), 1000 mg/m2 every 3 weeks until initial progression
- name
- Dacarbazine (DTIC)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- CROSSOVER
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 251
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Progression-free Survival (PFS) as Assessed by the Investigator
- time Frame
- 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)
- description
- 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.
- measure
- Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase
- time Frame
- 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)
- secondary Outcomes
- description
- 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.
- measure
- Overall Survival
- time Frame
- Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months)
- description
- 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.
- measure
- 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
- time Frame
- From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks)
- description
- 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.
- measure
- Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase
- time Frame
- From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks)
- description
- 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.
- measure
- Duration of Response as Assessed by the Investigator: Randomized Phase
- time Frame
- 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)
- description
- 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.
- measure
- Duration of Response as Assessed by an Independent Radiologist: Randomized Phase
- time Frame
- 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)
- description
- 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.
- measure
- Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase
- time Frame
- 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)
- description
- 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.
- measure
- 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
- time Frame
- From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months)
- description
- 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.
- measure
- Duration of Response as Assessed by the Investigator: Crossover Phase
- time Frame
- 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)
- description
- 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.
- measure
- Number of Participants With Non-melanoma Skin Lesions: Randomized Phase
- time Frame
- From Screening until study completion or discontinuation from the study (up to 9.9 months)
- description
- 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.
- measure
- Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay
- time Frame
- Screening
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- 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.
- pmid
- 22735384
- type
- BACKGROUND
- citation
- 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.
- pmid
- 31864178
- type
- DERIVED
- citation
- 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.
- pmid
- 26446943
- type
- DERIVED
- citation
- 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.
- pmid
- 26040620
- type
- DERIVED
- citation
- 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.
- pmid
- 24769640
- type
- DERIVED
- citation
- 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.
- pmid
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- type
- DERIVED
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- icacy of TAFINLAR as a single agent were evaluated in an international, multi-center, randomized (3:1), open-label, active-controlled trial (the BREAK-3 study; NCT01227889) conducted in 250 patients with previously untreated BRAF V600E mutation-positive, unresectable or metastatic melanoma. Patients with any prior use of BRAF inh
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- n orally available, small-molecule, selective BRAF inhibitor that was approved by the FDA in 2013. An international multicenter trial (<a href="/clinicaltrials/NCT01227889">BREAK-3</a> [NCT01227889]) showed that dabrafenib improved PFS when compared with dacarbazine.[<a href="#cit/section_4.26">26</a>]</p> </section>
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- molecule, selective BRAF inhibitor that was approved by the FDA in 2013. An international multicenter trial (<a href="/clinicaltrials/NCT01227889">BREAK-3</a> [NCT01227889]) showed that dabrafenib improved PFS when compared with dacarbazine.[<a href="#cit/section_4.26">26</a>]</p> </section> <section id="_1337
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- index="-1">Evidence (dabrafenib):</p> <div class="pdq-content-list"><ol id="_713"><li> An international multicenter trial (<a href="/clinicaltrials/NCT01227889">BREAK-3</a> [NCT01227889]) compared dabrafenib with dacarbazine. A total of 250 patients with unresectable stage III or IV melanoma and <em class="gene-name">
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Preserved source evidence · Not medical advice