NCT02367859

Brief Summary

This pilot clinical trial studies dabrafenib and trametinib in treating patients with ameloblastoma and a specific mutation (change) in the BRAF gene. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2017

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 13, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 20, 2015

Completed
2.4 years until next milestone

Study Start

First participant enrolled

July 17, 2017

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 5, 2018

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 26, 2019

Completed
7 months until next milestone

Results Posted

Study results publicly available

January 21, 2020

Completed
Last Updated

January 30, 2024

Status Verified

January 1, 2024

Enrollment Period

1.3 years

First QC Date

February 13, 2015

Results QC Date

December 12, 2019

Last Update Submit

January 7, 2024

Conditions

AmeloblastomaBRAF Gene Mutation

Keywords

ameloblastomaBRAFodontogenic canceradamantinoma

Outcome Measures

Primary Outcomes (1)

  • Tumor Response

    Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Overall tumor response was assessed as the number of participants achieving either a complete response (CR) or a partial response (PR). The criteria are: * CR = Disappearance of all target lesions * PR = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion.

    6 weeks

Secondary Outcomes (3)

  • Percent Tumor Necrosis

    6 weeks

  • Change in Proliferation

    6 weeks

  • Phosphorylation of Tumor Markers MEK and ERK

    6 weeks

Study Arms (1)

Treatment (dabrafenib)

EXPERIMENTAL

Patients receive dabrafenib PO BID every 12 hours plus trametinib daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression.

Drug: DabrafenibDrug: Trametinib

Interventions

DabrafenibDRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436, Tafinlar
Treatment (dabrafenib)
TrametinibDRUG

Given PO

Also known as: Mekinist
Treatment (dabrafenib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histological diagnosis of ameloblastoma; all stages are eligible; patients must have evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform, immunohistochemistry, Foundation One tests, etc.)
  • Life expectancy \> 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Absolute neutrophil count (ANC) \> 1.5 x10\^9/L
  • Platelet (PLT) \> 99 x 10\^9/L
  • Hemoglobin \> 8 g/dL
  • Total bilirubin (Tbili) \< 1.6 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 2.6 x ULN
  • Alkaline phosphatase (alk phos) \< 2.6 x ULN
  • Serum creatinine \< 1.6 x ULN or creatinine clearance \> 50 ml/min
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients of childbearing potential must agree to use effective contraception until at least 6 months after treatment with dabrafenib
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
  • Left ventricular ejection fraction equal to or greater than normal

You may not qualify if:

  • No prior treatment with agents targeting BRAF mutant tyrosine kinases or radiation of target lesions
  • Invasive malignancy other than ameloblastoma within 3 years, excluding curatively treated basal cell carcinoma, and other highly curable cancers such as early stage cutaneous squamous cell carcinoma (T1 NO) cervical carcinoma in situ (CIS), early stage prostate cancer, thyroid cancer or breast cancer
  • Uncontrolled hypertension, chronic heart failure (CHF), or other major medical illness
  • Prior allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib
  • Concomitant use of strong inhibitors (e.g., ketoconazole, nefazodone, clarithromycin, gemfibrozil) or strong inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St John's wort) of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8)
  • Concomitant use of proton pump inhibitors, H2-receptor antagonists, antacids
  • Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Pregnant or nursing patients; women of childbearing potential must have a negative pregnancy test within 14 days of enrollment
  • Electrocardiogram (EKG) with QTcB (Bazett's formula) \> 480 ms done within 14 days of enrollment
  • Interstitial lung disease or pneumonitis
  • A history of retinal vein occlusion (RVO)
  • Congestive heart failure NYHA class III or worse (Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.)
  • A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

Related Links

MeSH Terms

Conditions

AmeloblastomaAdamantinoma

Interventions

dabrafenibtrametinib

Condition Hierarchy (Ancestors)

Odontogenic TumorsNeoplasms by Histologic TypeNeoplasmsBone NeoplasmsNeoplasms by SiteBone DiseasesMusculoskeletal Diseases

Results Point of Contact

Title
Dr. A. Dimitrios Colevas, Professor of Medicine (Oncology)
Organization
Stanford University
colevas@stanford.edu
650-724-9707

Study Officials

  • Alexander Colevas

    Stanford University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine (Oncology) and Otolaryngology

Study Record Dates

First Submitted

February 13, 2015

First Posted

February 20, 2015

Study Start

July 17, 2017

Primary Completion

November 5, 2018

Study Completion

June 26, 2019

Last Updated

January 30, 2024

Results First Posted

January 21, 2020

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)