Dabrafenib Plus Trametinib in Patients With Advanced Solid Tumor Having BRAF V600E Mutation or Clinically Actionable BRAF Gene Alterations

NCT05876806 | Recruiting Phase 2

• 1 other identifier: BROAD
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, open-label, non-randomized, multi-center study of oral Dabrafenib in combination with oral Trametinib in subjects with solid tumors with BRAF V600E mutation or clinically actionable BRAF gene alterations.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  Disease control Rate (DCR) is defined as the proportion of subjects with objective evidence of complete response (CR), partial response (PR), or stable disease (SD).

  From study treatment start date until first documented complete response, partial response or stable disease, assessed up to 36 months

Secondary Outcomes (3)

• Overall Survival (OS)

  From study treatment start date until date of of death from any cause, assessed up to 36 months

• Progression Free Survival (PFS)

  From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 36 months

• Objective Response Rate (ORR)

  From study treatment start date until first documented complete response or partial response, assessed up to 36 months

Study Arms (1)

Dabrafenib + Trametinib

EXPERIMENTAL

Subjects will receive Dabrafenib 150 mg twice daily orally plus Trametinib 2 mg once daily orally on a continuous basis. A treatment cycle is 28 days in duration. Subjects will continue treatment until an unacceptable toxicity, disease progression, or death occurs.

Drug: Dabrafenib; Drug: Trametinib

Interventions

Dabrafenib DRUG

Dabrafenib is a 150 mg twice daily capsule administered orally on a continuous basis

Dabrafenib + Trametinib

Trametinib DRUG

Trametinib is a 2 mg once daily tablet administered orally on a continuous basis.

Dabrafenib + Trametinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all the following criteria for study entry:
• Patient who agreed to participate in the KOSMOS-II master observation study
• years of age or older
• Patients with BRAF V600 mutated advanced solid tumor (excluding BRAF V600E/K mutated malignant melanoma, BRAF V600E mutated non-small cell lung cancer, and BRAF V600E mutated colorectal cancer)
• Patients with other BRAF gene alterations that are regarded to be actionable by the KOSMOS MTB
• Disease progression after ≥ 1-prior line of systemic treatment and no standard treatment option
• ECOG performance status score 0-2
• Life expectancy of \> 3 months
• Measurable or evaluable disease according to RECIST version 1.1
• Ability to take oral medications
• Adequate bone marrow and organ function
• Patients who voluntarily decided to participate after understanding this clinical trial, and signed a written informed consent

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from study entry:
• Prior treatment with a BRAF inhibitor (including, but not limited to, dabrafenib, vemurafenib, encorafenib) or MEK inhibitor (including, but not limited to, trametinib, binimetinib, selumetinib, cobimetinib) or ERK inhibitor (including, but not limited to, ravoxertinib, ulixertinib, CC-90003, MK-8353)
• History of malignancies with confirmed activating RAS mutation.
• Hypersensitivity to the active ingredients and additives of investigational product.
• Presence of any unresolved ≥Grade 2 (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) toxicity from previous anti-cancer therapy at the time of enrollment. (Except toxicities which are not clinically significant such as alopecia, skin discoloration, and neuropathy).
• Any anti-cancer treatment (local treatment, chemotherapy, immunotherapy, targeted therapy) within 2 weeks prior to the start of study treatment.
• Prior major surgery less than 14 days before enrollment. Any surgery-related AE must have been resolved before enrollment.
• Prior radiotherapy less than 14 days before enrollment, except for ATC (radiotherapy is not permitted within 7 days before enrollment).
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. (Patient with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is potentially eligible).
• Presence of central nervous system metastases that are symptomatic or untreated or not stable for ≥3 months or requiring corticosteroids.
• Symptomatic or untreated leptomeningeal or spinal cord compression. Subjects who have been previously treated for these conditions are asymptomatic and currently not taking corticosteroids before enrollment, is permitted.
• Current evidence of cardiovascular risk including any of the following:
• Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal
• QT interval corrected for heart rate using Bazett's formula ≥ 480 msec
• Clinically significant uncontrolled arrhythmias

Sponsors & Collaborators

• Se Jun Park: lead

Study Sites (1)

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, 06591, South Korea

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

dabrafenib; trametinib

Study Officials

• Se Jun Park, MD, PhD

  The Catholic University of Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Se Jun Park, MD, PhD

CONTACT

82-2-2258-6757; psj6936@naver.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 25, 2023
• Study Start: June 20, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 30, 2023

Record last verified: 2023-11

Locations

KR (1)