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Continuous vs Intermittent Dabrafenib Plus Trametinib in BRAFV600 Mutant Stage 3 Unresectable or Metastatic Melanoma (INTERIM)

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: NCT03352947
Recruitment Status : Completed
First Posted : November 24, 2017
Last Update Posted : December 8, 2020
Sponsor:
Collaborators:
National Institute for Health Research, United Kingdom
Oxford University Hospitals NHS Trust
University of Oxford
Information provided by (Responsible Party):
CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust

Brief Summary:
This feasibility study aims to determine if intermittent dosing is deliverable, based on patient and professional willingness to take part in a randomised trial evaluating less rather than the standard durations of treatment. The trial will evaluate treatment compliance, Progression Free Survival and Quality of Life, to inform whether a subsequent definitive trial is justified and how it should be designed.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Dabrafenib Drug: Trametinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: INTERIM is a multi-centre, open label, two arm, randomised phase II feasibility trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INTERIM: a Randomised Phase II Feasibility Study of INTERmittent Versus Continuous Dosing or Oral Targeted Combination Therapy in Patients With BRAFV600 Mutant Stage 3 Unresectable or Metastatic Melanoma
Actual Study Start Date : November 3, 2017
Actual Primary Completion Date : March 31, 2020
Actual Study Completion Date : November 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Active Comparator: Continuous (Standard)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-28 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-28 of a 28 day cycle
Drug: Dabrafenib
150mg Dabrafenib twice daily day 1-21 of 28 day cycle in intermittent arm Day 1-28 of 28 day cycle in continuous arm
Other Name: Tafinlar

Drug: Trametinib
Trametinib 2mg once daily Day 1-14 of a 28 day cycle in intermittent arm Day 1-28 of a 28 day cycle in the continuous arm
Other Name: Mekinist

Experimental: Intermittent (experimental)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-21 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-14 of a 28 day cycle
Drug: Dabrafenib
150mg Dabrafenib twice daily day 1-21 of 28 day cycle in intermittent arm Day 1-28 of 28 day cycle in continuous arm
Other Name: Tafinlar

Drug: Trametinib
Trametinib 2mg once daily Day 1-14 of a 28 day cycle in intermittent arm Day 1-28 of a 28 day cycle in the continuous arm
Other Name: Mekinist




Primary Outcome Measures :
  1. Recruitment Rate [ Time Frame: To be assessed once the trial has been recruiting for 15 months, or when 15 sites have been open for 6 months whichever is sooner ]
    Average number of patients recruited per site per two months.

  2. Treatment compliance [ Time Frame: 6 months from randomisation ]
    percentage of patients completing the allocated treatment

  3. Overall Quality of Life [ Time Frame: 6 months from randomisation ]
    global health status score derived from (EORTC) QLQ-C30 questionnaire

  4. Progression Free survival [ Time Frame: calculated as the duration from the date of randomisation to the date of first progression or death from any cause, whichever occurs first, assessed up to 5 years ]
    Assessed according to standard Response Criteria in Solid Tumours (RECIST v1.1)


Secondary Outcome Measures :
  1. Incidence of treatment emergent adverse events (safety and tolerability) [ Time Frame: Through study completion, an average of 1 year ]
    Assess using standard cancer National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03)

  2. Objective response rate [ Time Frame: Through study completion, an average of 1 year ]
    assessed according to RECIST v1.1

  3. Time to treatment failure [ Time Frame: Through study completion, an average of 1 year ]
    Time from starting drug treatment (day 1, cycle 1) until day 1 of last cycle + 28 days

  4. Overall survival [ Time Frame: Assessed up to 5 years ]
    calculated as duration from date of randomisation to the date of death from any cause

  5. Patient Reported Outcomes focusing on skin toxicity evaluation [ Time Frame: Through study completion, an average of 1 year ]
    assessed using skin-specific patient reported outcome measures

  6. Patient Experience [ Time Frame: Surveys at screening and after 9 months. Interviews by invitation at a later date ]
    Surveys of patients in both arms of the trial. Semi-structured interview in a subset of patients.

  7. Impact on Quality of Life [ Time Frame: At 6 months from baseline ]
    Using EORTC QLQ-C30 questionnaire

  8. Health Economic Evaluation [ Time Frame: Through study completion, an average of 1 year ]
    Using EQ-5D 5L questionnaire


Other Outcome Measures:
  1. Kinetics of BRAF mutation load in each arm of the trial [ Time Frame: Through study completion, an average of 1 year ]
    using blood and tumour tissue taken from recruited patients

  2. Emerging genetic changes associated with acquired resistance [ Time Frame: Through study completion, an average of 1 year ]
    using blood and tumour tissue taken from recruited patients



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.


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

Inclusion Criteria:

  • Signed informed consent
  • Age ≥18 years old
  • Histologically or cytologically confirmed BRAFV600 mutant stage 3 unresectable or metastatic melanoma
  • Measurable disease by RECIST
  • ECOG performance status 0-2
  • Minimum life expectancy 12 weeks
  • Adequate bone marrow, renal and liver function
  • Received no prior BRAF or MEK inhibitor therapy for metastatic disease
  • Willing and able to comply with the scheduled visits, treatment plans, laboratory tests, completion of QoL questionnaires and other study procedures
  • Archival tumour tissue sample available
  • Women of child-bearing potential and all sexually active male patients must agree to use effective contraception methods throughout treatment

Exclusion Criteria:

  • Concomitant immunotherapy being administered to treat advanced melanoma
  • Other invasive malignancies diagnosed within the last year which are not in complete remission, or for which additional therapy is required
  • Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial
  • Women who are pregnant, plan to become pregnant or are lactating during the trial period
  • Other investigational anti-cancer drugs
  • Use of strong inducers and inhibitors of CYP3A or CYP2C8

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): NCT03352947


Locations
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United Kingdom
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
National Institute for Health Research, United Kingdom
Oxford University Hospitals NHS Trust
University of Oxford
Investigators
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Principal Investigator: Pippa Corrie, FRCP Addenbrookes
  Study Documents (Full-Text)

Documents provided by CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust:
Study Protocol  [PDF] September 21, 2017

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Responsible Party: CCTU- Cancer Theme, Consultant and Associate Lecturer in Medical Oncology, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03352947    
Other Study ID Numbers: INTERIM
2016-005228-27 ( EudraCT Number )
PB-PG-0815-20048 ( Other Grant/Funding Number: NIHR )
First Posted: November 24, 2017    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: PID will not be shared with other researchers. PID will not be moved from participating sties. Patient will be identified by their initials, date of birth and trial number.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action