[18F]Dabrafenib Molecular Imaging in Melanoma Brain Metastasis

NCT02700763 | Terminated

• 1 other identifier: 201600134
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In this feasibility study, \[18F\]dabrafenib will be used as radioactive tracer. All patients in this study are diagnosed with advanced melanoma with evidence of brain metastases and are eligible for treatment with dabrafenib, a specific V600-mutated BRAF inhibitor. Patients will undergo a dynamic PET scan of the brain to determine \[18F\]dabrafenib distribution and kinetics in brain metastases. In addition, a static total body PET scan will be performed to visualize whole body distribution and tracer uptake.

Conditions

Melanoma

Keywords

Brain metastasis

Outcome Measures

Primary Outcomes (1)

• Absolute uptake of [18F]dabrafenib

  Determination of the absolute uptake (Standard uptake value (SUV)) and kinetics (time-activity curves, volume of distribution) of \[18F\]dabrafenib in normal brain and brain metastasis.

  60 minutes

Secondary Outcomes (7)

• Heterogeneity of [18F]dabrafenib uptake of tumor lesions and kinetics in the brain

  Baseline

• Intra-patient heterogeneity in [18F]dabrafenib uptake of tumor lesions

  Baseline

• Inter-patient heterogeneity in [18F]dabrafenib uptake of tumor lesions

  baseline

• Correlation of [18F]dabrafenib uptake with response to dabrafenib treatment of tumor lesions

  4 weeks

• Correlation between absolute tumor tracer uptake of [18F]dabrafenib and immunohistochemical staining with VE1 mAb (anti V600-mutated BRAF).

  Baseline

Study Arms (1)

[18F]dabrafenib molecular imaging

EXPERIMENTAL

A \[18F\]dabrafenib PET scan will be performed at baseline (7 days or less before the start of treatment with oral dabrafenib).

Other: [18F]dabrafenib molecular imaging

Interventions

[18F]dabrafenib molecular imaging OTHER

A \[18F\]dabrafenib dynamic PET scan of the brain (60 minutes) and static total body PET scan will be performed at baseline.

[18F]dabrafenib molecular imaging

Eligibility Criteria

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

You may qualify if:

• Has signed informed consent.
• Age \>=18 years of age.
• Histologically confirmed cutaneous metastatic melanoma (Stage IV), including confirmed brain metastases.
• BRAF mutation-positive (V600 E/K) melanoma as determined by standardized genetic testing.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eligible for treatment with dabrafenib. Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the study treatment that may impact subject eligibility is provided in the summary of product characteristics (SPC) for Tafinlar.
• No contraindication for performing a CT scan.
• No contraindications for performing an MRI scan of the brain.
• Able to swallow and retain oral medication.
• Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control, as defined in Section 5.2, from 14 days prior to randomization, throughout the treatment period and for 4 weeks after the last dose of study treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Must have adequate organ function as defined in Table 1. Table 1 Definitions for Adequate Baseline Organ Function System Laboratory Values Hematologic ANC \>= 1.2 × 109/L Hemoglobin \>= 9 g/dL Platelet count \>= 75 x 109/L PT/INRa and PTT \<= 1.3 x ULN Hepatic Total bilirubin \<= 1.5 x ULN AST and ALT \<= 2.5 x ULN Renal Serum creatininec \<= 1.5 mg/dL Cardial ECG QTc \< 480 msec Abbreviations: ALT = alanine transaminase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ECG = electrocardiogram; INR = international normalized ratio; PT = prothrombin time; PTT = partial thromboplastin time; ULN = upper limit of normal.
• Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to randomization.
• Except subjects with known Gilbert's syndrome.
• If serum creatinine is \> 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be \>= 50 mL/min to be eligible.

You may not qualify if:

• Previous treatment with a BRAF or MEK inhibitor. (previous systemic treatment for melanoma with other agents is allowed).
• Previous brain surgery or radiotherapy to the brain.
• Cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, vaccine therapy or major surgery) or investigational anti-cancer drugs within the last 3 weeks, or chemotherapy without delayed toxicity within the last 2 weeks, preceding the first dose of dabrafenib.
• Current use of a prohibited medication or requires any of these medications during treatment with dabrafenib as mentioned in the SPC for Tafinlar.
• Current use of oral anticoagulant therapy. NOTE: Prophylactic low-dose of low molecular weight heparin (LMWH) is permitted.
• Known immediate or delayed hypersensitivity reaction to dabrafenib or excipients.
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study.
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (26) grade 2 or higher from previous anti-cancer therapy, except alopecia.
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, the Novartis medical monitor will be contacted.
• Presence of malignancy other than disease under study within 5 years of study enrollment, or any malignancy with confirmed activating RAS mutation. Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Leptomeningeal metastases, brain metastases, or metastases causing spinal cord compression that are symptomatic or not stable for \>=4 weeks or requiring corticosteroids. Subjects on a stable dose of corticosteroids \>1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of the Novartis medical monitor.
• A history or evidence of cardiovascular risk including any of the following:
• A QT interval corrected for heart rate using the Bazett's formula \>=480 msec;
• A history or evidence of current clinically significant uncontrolled arrhythmias;
• A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Geke AP Hospers, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: March 7, 2016
• Study Start: December 6, 2016
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: May 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)