Comparative Effectiveness of Targeted Therapies in BRAF Positive Metastatic Melanoma in the US (OCEANMIST)

• ClinicalTrials.gov Identifier: NCT05260684
• Recruitment Status: Active, not recruiting
• First Posted: March 2, 2022
• Last Update Posted: March 2, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This study aims to compare real-world effectiveness of BRAF/MEK inhibitors in BRAF-mutant metastatic melanoma patients in the United States by line of therapy.

The Flatiron Health electronic health record (EHR) data from US cancer clinics will be used for this retrospective database analysis.

Condition or disease	Intervention/treatment
Melanoma	Drug: Encorafenib; Drug: Binimetinib; Drug: Vemurafenib; Drug: Cobimetinib; Drug: Dabrafenib; Drug: Trametinib

Study Design

• Study Type: Observational
• Actual Enrollment: 1 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Comparative Effectiveness of Different Targeted Therapies for BRAF-mutated Unresectable/Metastatic Melanoma in the United States
• Actual Study Start Date: January 17, 2022
• Estimated Primary Completion Date: July 1, 2024
• Estimated Study Completion Date: July 1, 2024

Groups and Cohorts

Group/Cohort	Intervention/treatment
Encorafenib + binimetinib; Encorafenib 450 mg once a day (QD) Binimetinib 45 mg twice a day (BID)	Drug: Encorafenib; 450 mg QD; Other Name: Administration route: Oral; Drug: Binimetinib; 45 mg BID; Other Name: Administration route: Oral
Vemurafenib + binimetinib; Vemurafenib 960 mg twice a day (BID) for 28 days of 28 day cycle Cobimetinib 60 mg once a day (QD) for 21 days of 28 day cycle	Drug: Vemurafenib; 960 mg BID for 28 days/cycle; Other Name: Administration route: Oral; Drug: Cobimetinib; 60 mg QD for 21 days/cycle; Other Name: Administration route: Oral
Dabrafenib + trametinib; Dabrafenib 150 mg twice a day (BID) Trametinib 2 mg once a day (QD)	Drug: Dabrafenib; 150 mg BID; Other Name: Administration route: Oral; Drug: Trametinib; 2 mg QD; Other Name: Administration route: Oral

Outcome Measures

Primary Outcome Measures :

1. real-world Progression Free Survival (rwPFS) [ Time Frame: From index date to either date of first progression or death, whichever comes first, assessed up to 52 months ]
   Time to event (months). Length of time from index date to either the date of first progression event or death in the absence of progression. rwPFS will be analyzed by line of therapy. Patients without a progression or death date more than 14 days after the index date will be censored at the last date the patient could have been assessed for progression (eg, last clinical note date).
2. real-world Overall Survival (rwOS) [ Time Frame: From index date to death, assessed up to 52 months ]
   Time to event (months). Length of time from index date to the date of death. Patients without a date of death will be censored at their last known activity.
3. real-world Complete Response (rwCR) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]
   Categorical variable. Complete resolution of disease. Categorical response to therapy observed after start of therapy at each assessment time point.
4. real-world Partial Response (rwPR) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]
   Categorical variable. Partial reduction in tumor burden in some or all areas without any areas of increasing disease over observation period. rwPR captures a decrease in disease burden even though disease is still present.
5. real-world Stable Disease (rwSD) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]
   Categorical variable No change in overall disease burden over observation period, rwSD is also used to capture mixed response (some lesions increased, some lesions decreased).
6. real-world Progressed Disease (rwPD) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]
   Categorical variable Increase in disease and/or presence of any new lesions over observation period.
7. Duration of therapy (DoT) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]

   Continuous (months) Length of time from the start of a treatment to the time of treatment discontinuation for any reason, within a given line of therapy (LOT) (eg, time from therapy start to treatment discontinuation, therapy change [next LOT - switch or augment], or death).

   Calculated within each LOT in scope (eg, for first line and for second line separately). Start date is the earliest of all drug episodes across all drugs in the LOT.

   The end date of the first LOT is the day before the start date of the second LOT.

   The end date of the second LOT is defined as the earliest of either:

   1. The most recent administration or visit date
   2. When available, the abstracted end date for the oral span is used as the LOT end date
   3. The date of death, if applicable (Note that for patient privacy and de-identification purposes, date of death is generalized to the last day of the month of death).
8. Time off treatment (ToffT) [ Time Frame: From index date to start date of next line of therapy, most recent administration/visit date, abstracted end date for the oral span, or date of death, whichever came first, assessed up to 52 months ]
   Continuous (months) Length of time between date where the first line of therapy is discontinued to date where the second line of therapy is initiated.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study population will be derived from an anonymized data available in the Advanced Melanoma (AMel) Flatiron Health database.

Criteria

Inclusion Criteria:

• Index date: First line therapy start date recorded in the database between 20 November 2015 and 03 January 2022
• Age 18 years or older in the year of the index first m-melanoma diagnostic claim
• Patients with pathologic stages III to IV at initial diagnosis on or after 01 January 2011, or patients who develop a locoregional or distant recurrence on or after 01 January 2011
• Patients with confirmed BRAF V600 activating mutation will be included - BRAF mutational testing / genetic analysis results needed (testing status, mutation type, test result). Patients having tested positive for the mutation at any time will be included. Date of sample collection and date of test result received by provider will be collected

Exclusion Criteria:

• Patients with a record of other primary malignant tumors in the year before diagnosis of m-melanoma
• Patients with only 1 m-melanoma diagnosis
• Patients with insufficient data for analysis (ie, <1 month of clinical activity during the prior period, had <1 month of clinical activity during the post period)
• Patients currently enrolled in a clinical trial
• Patients that received treatment for m-melanoma prior to the study index date

Contacts and Locations

Locations

United States, New York

Pfizer Investigational Site

New York, New York, United States, 10017

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05260684
• Other Study ID Numbers: C4221028; OCEANMIST ( Other Identifier: Alias Study Number )
• First Posted: March 2, 2022
• Last Update Posted: March 2, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Keywords provided by Pfizer:

BRAF-mutant; Metastatic melanoma

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Trametinib; Vemurafenib; Dabrafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action