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Trial record 1 of 1 for:    combi-aplus | Sweden
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Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes (COMBI-APlus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03551626
Recruitment Status : Active, not recruiting
First Posted : June 11, 2018
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 30, 2018
First Posted Date  ICMJE June 11, 2018
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE August 29, 2018
Estimated Primary Completion Date March 16, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2018)
Change from baseline in composite rate of pyrexia related events [ Time Frame: Baseline up to 12 months ]
The composite rate of grade 3/4 pyrexia, ospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated subjects
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2018)
  • Relapse free survival (RFS) from the first dose to disease recurrence or death from any cause [ Time Frame: Baseline up to approximately 24 months ]
    RFS is defined as the time from the date of first dose of the study medication to the date of disease recurrence or death due to any cause.
  • Overall Survival (OS) from the first dose to date of death due to any cause [ Time Frame: Baseline up to approximately 24 months ]
    OS is defined as the time from date of the first dose of study medication to date of death due to any cause.
  • Percentage of patients who require management of pyrexia [ Time Frame: Baseline up to 12 months ]
    Percentage of patients who experienced pyrexia and required intervention
  • The percentage of participants who permanently discontinued treatment due to any Adverse event [ Time Frame: Baseline up to 12 months ]
    Participants who permanently discontinued treatment due to any Adverse event during treatment
  • Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M MS) [ Time Frame: Baseline up to 24 months ]
    QoL assessed using Function Assessment Cancer Therapy-melanoma (FACT-M) assessment tool. This includes the FACT-Melanoma subscale (FACT-M MS) questionnaire -specific subscale consists of 16 questions for Melanoma Subscale (MS) and 8 questions for Melanoma Surgery Scale (MSS).Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes
Official Title  ICMJE COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)
Brief Summary

This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes.

Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm.

This study consists of two Periods for Enrolled subjects:

  • Treatment Period - subjects will receive up to 12 months of treatment.
  • Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Melanoma
Intervention  ICMJE
  • Drug: Dabrafenib
    Supplied as dabrafenib 50 mg, 75 mg Capsules for oral use
  • Drug: Trametinib
    supplied as trametinib 0.5mg, 2.0mg tablets for oral use
Study Arms  ICMJE Experimental: Dabrafenib and trametinib combination therapy
Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
Interventions:
  • Drug: Dabrafenib
  • Drug: Trametinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 18, 2020)
557
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2018)
600
Estimated Study Completion Date  ICMJE October 22, 2021
Estimated Primary Completion Date March 16, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]
  • V600E/K mutation positive using a validated local test
  • Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  • Subjects who have previously had Stage III melanoma at any time are not eligible.
  • Subjects with an unknown primary melanoma are not eligible.
  • Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Exclusion Criteria:

  • Uveal or mucosal melanoma
  • Evidence of metastatic disease including unresectable in-transit metastasis
  • Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
  • History or current evidence of cardiovascular risk
  • A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden,   Argentina,   Australia,   Brazil,   Canada,   Czechia,   Finland,   France,   Greece,   Hungary,   Israel,   Italy,   Japan,   Latvia,   Lithuania,   Norway,   Poland,   Portugal,   Russian Federation,   Slovakia,   Slovenia,   Turkey,   United Kingdom
Removed Location Countries Belgium
 
Administrative Information
NCT Number  ICMJE NCT03551626
Other Study ID Numbers  ICMJE CDRB436F2410
2018-000168-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP