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

NCT03352947 | Completed Phase 2 DMC

• 3 other identifiers: INTERIM2016-005228-27PB-PG-0815-20048
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (4)

• Recruitment Rate

  Average number of patients recruited per site per two months.

  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

• Treatment compliance

  percentage of patients completing the allocated treatment

  6 months from randomisation

• Overall Quality of Life

  global health status score derived from (EORTC) QLQ-C30 questionnaire

  6 months from randomisation

• Progression Free survival

  Assessed according to standard Response Criteria in Solid Tumours (RECIST v1.1)

  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

Secondary Outcomes (8)

• Incidence of treatment emergent adverse events (safety and tolerability)

  Through study completion, an average of 1 year

• Objective response rate

  Through study completion, an average of 1 year

• Time to treatment failure

  Through study completion, an average of 1 year

• Overall survival

  Assessed up to 5 years

• Patient Reported Outcomes focusing on skin toxicity evaluation

  Through study completion, an average of 1 year

Other Outcomes (2)

• Kinetics of BRAF mutation load in each arm of the trial

  Through study completion, an average of 1 year

• Emerging genetic changes associated with acquired resistance

  Through study completion, an average of 1 year

Study Arms (2)

Continuous (Standard)

ACTIVE COMPARATOR

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; Drug: Trametinib

Intermittent (experimental)

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; Drug: Trametinib

Interventions

Dabrafenib DRUG

150mg Dabrafenib twice daily day 1-21 of 28 day cycle in intermittent arm Day 1-28 of 28 day cycle in continuous arm

Also known as: Tafinlar

Continuous (Standard); Intermittent (experimental)

Trametinib DRUG

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

Also known as: Mekinist

Continuous (Standard); Intermittent (experimental)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• University of Oxford: collaborator

Study Sites (1)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Pippa Corrie, FRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant and Associate Lecturer in Medical Oncology

Model Details: INTERIM is a multi-centre, open label, two arm, randomised phase II feasibility trial

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 24, 2017
• Study Start: November 3, 2017
• Primary Completion: March 31, 2020
• Study Completion: November 27, 2020
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)