pRospective Evaluation of Clinical Outcomes in Patients With metAsTatIс melanOma Treated With dabrafeNib and trAmetinib in reaL practicE (RATIONALE)

May 29, 2022 updated by: MelanomaPRO, Russia

Prospective Evaluation of Clinical Outcomes in Patients With Resectable or Metastatic BRAF+ Melanoma Treated With Dabrafenib and Trametinib in Real Practice

Prospective evaluation of clinical outcomes in patients with resectable or metastatic BRAF+ melanoma treated with dabrafenib and trametinib in real practice

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Rationale and background It is now accepted by the majority of experts in oncology that most effective and safe therapy options should be considered for first-line treatment, including adjuvant setting. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures used in clinical trials, post-authorization "real-world" data are important to quantify feasibility, acceptance, and practical considerations on prescription of targeted therapy with Dabrafenib+Trametinib. Therefore, it is of great interest for clinical and scientific communities to evaluate patient and treatment choice used in routine practice of Russian oncology centers. The aim of this study is to asses clinical outcomes of patient receiving Dab+Tram in different substages of resectable melanoma and different lines in metastatic melanoma., Additionally, it is of interest to gain insights into real world data regarding quality of life of melanoma patients treated with Dabrafenib and Trametinib in adjuvant or metastatic setting.

Research question and objectives Primary objective The primary objective in the study is to estimate relapse-free survival (RFS) in melanoma patients in adjuvant settings and progression free survival (PFS) in melanoma patients in metastatic settings. Primary endpoints

• The primary efficacy endpoint of the study is 12-month RFS rate, definded as the time form index date to the date of first documented relapse or death due to any cause.

The primary efficacy endpoint of the study is 12-month PFS rate, defined as the time from the index date to the date of the first documented progression by investigator judgement or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last tumor assessment

Secondary objectives

  • To describe patient populations receiving dabrafenib and trametinib for stage III resectable melanoma with respect to demographics and clinical characteristics at index date (baseline).
  • To describe patient populations receiving dabrafenib and trametinib for stage IV metastatic melanoma with respect to demographics and clinical characteristics at index date (baseline).
  • Evaluate retrospectively the sequence of therapy prior to initiating treatment with Dabrafenib and Trametinib.
  • Analyze prospectively treatment options following disease recurrence or progression on treatment with Dabrafenib and Trametinib.
  • Analyze proportion (%) of patients receiving adjuvant therapy with Dabrafenib and Trametinib for melanoma stage IIIA/IIIB/IIIC/IIID
  • Analyze proportion (%) of patients receiving Dabrafenib and Trametinib in 1L/2L/3L/later lines in metastatic settings.
  • Assess clinical outcomes (including treatment duration, treatment discontinuation rate) in melanoma patients treated with Dabrafenib and Trametinib in adjuvant settings in real-world practice.
  • Assess clinical outcomes in melanoma patients treated with Dabrafenib and Trametinib in metastatic settings (including median PFS, treatment duration, RR and) in real-world practice.
  • Assess safety of therapy of interest: rate of adverse events associated with the therapy, proportions of patients and reasons of dose adjustment on dabrafenib and trametinib, discontinuation rate and reasons of discontinuation in melanoma patients treated with Dabrafenib and Trametinib in adjuvant and metastatic in real-world practice.
  • Describe changes in patient-reported symptoms and quality of life (QoL) in melanoma patients treated with Dabrafenib and Trametinib in real-world setting.

Study design Patients will attend study sites in accordance with routine clinical practice. It is assumed that visits will performed every 3-4 months, as it is stated by the current guidelines (1). Patients will undergo standard procedures and tests according to clinical guidelines and physician's judgement (1). Available data from routine clinical management of the patients will be collected in the course of visits to investigation site.

The supposed duration of observation within the study is 1 year which corresponds to the requested duration of adjuvant therapy and is in line with the median PFS - 11.1 months according to the COMBI D/V trials' analysis for dabrafenib+trametinib therapy in the first line treatment of metastatic cutaneous melanoma with BRAF mutation (2). The enrollment period will continue for two years.

Baseline assessments will include collection of patient demographic data, disease history, treatment history, laboratory data and physical examination results as assessed by clinicians and patient reported outcomes (PROs) for symptoms and QoL. Treatment history will include all pharmacological therapy, its duration, response duration, reason for discontinuation. QoL assessment is not a part of routine practice for some investigation sites, hence, QoL will be evaluated if it does not interfere routine practice.

At each following visit (as indicated above, approximately each 3-4 months up to 1 year) available information on treatment status, response and progression, PROs, patient performance status and any relevant adverse occurrences will be collected.

Setting and study population This study is planned as a prospective non-interventional multicenter study. This study is observational in nature and does not impose a therapy protocol, diagnostic/therapeutic interventions or a visit schedule. Patients with resectable or metastatic BRAF+ melanoma, in that treatment with dabrafenib and trametinib was initiated, either newly diagnosed or progressive during prior lines of therapy, will be included into the study. Initiation of dabrafenib+trametinib therapy will be considered an index event.

Adult patients receiving dabrafenib and trametitnib for adjuvant or metastatic melanoma treatment will be enrolled into study.

Variables All data will be collected in the course of prospective visits of patient to the clinical site according to routine practice. Demographic, disease and treatment-related variables will be collected in order to ensure completeness of data for endpoint analysis. Definitions of variables for analysis will be given in the relevant section of protocol.

Data sources Medical records and other disease-related documents will be used in the study.

Study size This study does not test any pre-defined statistical hypotheses therefore sample size and power calculation projections are not applicable. Since there is no formal hypothesis-testing, sample size for this study is based on the feasibility of enrolling the desired population during the enrolment period for this study.

Data analysis This is an exploratory study and no comparative analysis is planned. Descriptive statistics will be tabulated for the demographic and clinical characteristics and outcome variables. In all cases, point estimates as well as the corresponding two-sided 95% CI will be presented. No missing value imputation will be performed.

Kaplan-Meier method will be used for the analysis of time-to-event.

Milestones

Planned dates of study milestones:

Concept approved: 29 April 2021 Final protocol approval: 30 June 2021 Start of data collection (FPFV): 30 September 2021 End of enrollment (LPFV): 30 September 2023 End of primary data collection (LPLV): 30 September 2024 Final report on study results: 30 April 2025 Publication of study results: 30 September 2025

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Russian Federation
      • Ivanovo, Russian Federation, 153040
        • Recruiting
        • Ivanovo Regional Oncological Dispensary
        • Contact:
      • Krasnoyarsk, Russian Federation, 660133
        • Recruiting
        • KGBUZ "Krasnoyarsk regional clinical oncological dispensary named after A.I. A.I. Kryzhanovsky"
        • Contact:
      • Moscow, Russian Federation, 114578
        • Recruiting
        • N.N. Blokhin Russian Cancer Research Center
        • Contact:
        • Contact:
      • Moscow, Russian Federation, 129090
        • Recruiting
        • Moscow City Clinical Oncology Hospital No. 1
        • Contact:
      • Omsk, Russian Federation, 644013
        • Recruiting
        • Omsk Regional Clinical Oncology Center
        • Contact:
      • Perm, Russian Federation, 614066
        • Recruiting
        • Perm Regional Oncological Dispensary
        • Contact:
      • Tambov, Russian Federation, 392000
        • Recruiting
        • Tambov Regional Oncological Clinical Dispensary
        • Contact:
      • Yekaterinburg, Russian Federation, 620043
        • Not yet recruiting
        • Sverdlovsk Regional Oncology Center
        • Contact:
      • Yuzhno-Sakhalinsk, Russian Federation, 693010
        • Recruiting
        • GBUZ Yuzhno-Sakhalinsk oncologic dispensary
        • Contact:
          • Elvira Parsadanova, MD
          • Phone Number: 8 (424) 276-23-24
          • Email: 2903410@mail.ru
    • Alatai
      • Barnaul, Alatai, Russian Federation, 656000
        • Recruiting
        • Altai Regional Oncological Dispensary
        • Contact:
    • Chuvash Republic,
      • Cheboksary, Chuvash Republic,, Russian Federation, 428020
        • Recruiting
        • Republican Clinical Oncology Center of Chuvashia
        • Contact:
    • Irkutsk Region
      • Irkutsk, Irkutsk Region, Russian Federation, 664035
        • Recruiting
        • Irkutsk Regional Oncological Dispensary
        • Contact:
    • Rostov
      • Rostov-on-Don, Rostov, Russian Federation, 344006
        • Recruiting
        • Rostov Regional Oncological Dispensary
        • Contact:
    • THE Republic OF Mordovia
      • Saransk, THE Republic OF Mordovia, Russian Federation, 430032
        • Recruiting
        • State Budget Health Institution of the Republic of Mordovia "Republican Oncological Dispensary"
        • Contact:
    • The Udmurt Republic
      • Izhevsk, The Udmurt Republic, Russian Federation, 426009
        • Recruiting
        • Republican Clinical Oncological Dispensary named after Sergei Grigoryevich Primushko Ministry of Health of the Udmurt Republic
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Study will be conducted in investigation sites specialized in treatment of solid neoplasm or, more narrowed, melanoma. Patient may be enrolled either by surgical or medical oncologist if relevant indormation is available and there is no obvious risk for loss of contact with patient. Study population will be formed of the patients from cancer treatment facilities and the representativeness of sample may vary depending on participating sites. Study is going ro include patients receiving treatment of interest (dabrafenib and trametinib) for either adjuvant of metastatic setting of melanoma treatment.

Description

Inclusion Criteria:

  • Male or female patients aged 18 years or older;
  • Histologically confirmed stage III resectable or stage IV metastatic cutaneous melanoma with confirmed BRAF mutation, for whom the treating physician took the decision to initiate treatment with dabrafenib and trametinib before entering the study;
  • Treatment with Dabrafenib and Trametinib was initiated no longer than 4 weeks (28 days) prior to written informed consent for this study;
  • Performance status ≤ 2 by Eastern Cooperative Oncology Group (ECOG) scale;
  • Patient is willing and able to participate in the study;
  • Written informed consent for study participation.

Exclusion Criteria:

  • Patients with a life expectancy of less than 3 months at the time of melanoma diagnosis, per the investigator's judgment.
  • Patients participating in any interventional clinical trial that includes investigational or marketed products at the time of enrollment. (Patients participating in other investigator initiated or other non-interventional study [NIS] can be included as long as their standard of care is not altered by the study).
  • Patients on active treatment for malignancies other than melanoma at the time of enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Adjuvant cohort
Patients with resectable stage III melanoma, reciveng dabrafenib and trametinib in adjuvant settings
Drug: Dabrafenib
Observational stusy. No intervention is planned
Drug: Trametinib
Observational stusy. No intervention is planned
Metastatic cohort
Patients with unresectable stage IIIC/D or stage IV melanoma, reciveng dabrafenib and trametinib in metastatic settings
Drug: Dabrafenib
Observational stusy. No intervention is planned
Drug: Trametinib
Observational stusy. No intervention is planned

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
12-month RFS rate
Time Frame: 12 months
The primary efficacy endpoint of the study is 12-month RFS rate, definded as the time form index date to the date of first documented relapse or death due to any cause
12 months
12-month PFS rate
Time Frame: 12 months
The primary efficacy endpoint of the study is 12-month PFS rate, defined as the time from the index date to the date of the first documented progression by investigator judgement or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last tumor assessment
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To describe patient populations receiving dabrafenib and trametinib for stage III resectable melanoma with respect to demographics and clinical characteristics at index date (baseline).
Time Frame: 12 months
12 months
To describe patient populations receiving dabrafenib and trametinib for stage IV metastatic melanoma with respect to demographics and clinical characteristics at index date (baseline)
Time Frame: 12 months
12 months
Evaluate retrospectively the sequence of therapy prior to initiating treatment with Dabrafenib and Trametinib
Time Frame: 12 months
12 months
Analyze prospectively treatment options following disease recurrence or progression on treatment with Dabrafenib and Trametinib
Time Frame: 12 months
12 months
Analyze proportion (%) of patients receiving adjuvant therapy with Dabrafenib and Trametinib for melanoma stage IIIA/IIIB/IIIC/IIID
Time Frame: 12 months
12 months
Analyze proportion (%) of patients receiving Dabrafenib and Trametinib in 1L/2L/3L/later lines in metastatic settings
Time Frame: 12 months
12 months
To assess treatment duration in melanoma patients treated with Dabrafenib and Trametinib in adjuvant settings in real-world practice
Time Frame: 12 months
12 months
To assess treatment discontinuation rat in melanoma patients treated with Dabrafenib and Trametinib in adjuvant settings in real-world practice
Time Frame: 12 months
12 months
To assess median PFS in melanoma patients treated with Dabrafenib and Trametinib in metastatic settings in real-world practice
Time Frame: 12 months
12 months
To assess median treatment duration in melanoma patients treated with Dabrafenib and Trametinib in metastatic settings in real-world practice
Time Frame: 12 months
12 months
To assess treatment discontinuation rate in melanoma patients treated with Dabrafenib and Trametinib in metastatic settings in real-world practice
Time Frame: 12 months
12 months
To assess rate of adverse events associated with the therapy of interest
Time Frame: 12 months
12 months
To assess proportions of patients and reasons of dose adjustment on dabrafenib and trametinib in melanoma patients treated with Dabrafenib and Trametinib in adjuvant and metastatic in real-world practice
Time Frame: 12 months
12 months
Description of changes in patient-reported symptoms and quality of life (QoL) in melanoma patients treated with Dabrafenib and Trametinib in real-world setting
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MelanomaPRO, Russia

Collaborators

Novartis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2021

Primary Completion (Anticipated)

September 30, 2023

Study Completion (Anticipated)

September 30, 2024

Study Registration Dates

First Submitted

September 27, 2021

First Submitted That Met QC Criteria

December 23, 2021

First Posted (Actual)

December 28, 2021

Study Record Updates

Last Update Posted (Actual)

June 1, 2022

Last Update Submitted That Met QC Criteria

May 29, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDRB436ARU01R / MELPRO-0721

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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