Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03551626
Recruitment Status : Recruiting
First Posted : June 11, 2018
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Malignant Melanoma Drug: Dabrafenib Drug: Trametinib Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 25, 2018
Estimated Primary Completion Date : March 16, 2021
Estimated Study Completion Date : October 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever Melanoma

Arm Intervention/treatment
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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03551626


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +81337978748

  Show 97 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03551626     History of Changes
Other Study ID Numbers: CDRB436F2410
2018-000168-27 ( EudraCT Number )
First Posted: June 11, 2018    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
dabrafenib
trametinib
adjuvant
melanoma
combination treatment
pyrexia

Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Fever
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Body Temperature Changes
Signs and Symptoms
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action