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History of Changes for Study: NCT03551626
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)
Latest version (submitted October 14, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 28, 2018 None (earliest Version on record)
2 September 13, 2018 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 September 30, 2018 Contacts/Locations and Study Status
4 October 9, 2018 Study Status and Contacts/Locations
5 October 10, 2018 Contacts/Locations and Study Status
6 October 11, 2018 Contacts/Locations and Study Status
7 October 18, 2018 Contacts/Locations and Study Status
8 October 25, 2018 Contacts/Locations and Study Status
9 October 30, 2018 Contacts/Locations and Study Status
10 November 7, 2018 Study Status and Contacts/Locations
11 November 15, 2018 Contacts/Locations and Study Status
12 December 8, 2018 Study Status and Contacts/Locations
13 December 14, 2018 Contacts/Locations and Study Status
14 December 15, 2018 Contacts/Locations, Eligibility, Study Description and Study Status
15 February 8, 2019 Study Status and Contacts/Locations
16 March 1, 2019 Contacts/Locations and Study Status
17 April 15, 2019 Contacts/Locations and Study Status
18 April 18, 2020 Recruitment Status, Contacts/Locations, Study Status and Study Design
19 September 2, 2020 Contacts/Locations, Study Status, Eligibility, Outcome Measures and Conditions
20 April 12, 2021 Study Status, Contacts/Locations and Study Design
21 April 30, 2021 Study Status
22 May 5, 2021 Study Status
23 May 26, 2021 Study Status
24 August 2, 2021 Study Status
25 September 1, 2021 Contacts/Locations and Study Status
26 October 14, 2021 Recruitment Status, Study Status and Contacts/Locations
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Study NCT03551626
Submitted Date:  May 28, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: CDRB436F2410
Brief Title: 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)
Official Title: 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)
Secondary IDs: 2018-000168-27 [EudraCT Number]
Open or close this module Study Status
Record Verification: May 2018
Overall Status: Not yet recruiting
Study Start: September 21, 2018
Primary Completion: February 25, 2021 [Anticipated]
Study Completion: August 25, 2021 [Anticipated]
First Submitted: April 30, 2018
First Submitted that
Met QC Criteria:
May 28, 2018
First Posted: June 11, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
May 28, 2018
Last Update Posted: June 11, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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:
Open or close this module Conditions
Conditions: Malignant Melanoma
Keywords: dabrafenib
trametinib
adjuvant
melanoma
combination treatment
pyrexia
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 600 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Dabrafenib and trametinib combination therapy
Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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
Secondary Outcome Measures:
1. 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.
2. 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.
3. Percentage of patients who require management of pyrexia
[ Time Frame: Baseline up to 12 months ]

Percentage of patients who experienced pyrexia and required intervention
4. 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
5. 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Completely resected (R0) 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 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 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
Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: +41613241111
Email: novartis.email@novartis.com
Central Contact Backup: Novartis Pharmaceuticals
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Links:
Available IPD/Information:

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