E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)

NCT03332589 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: STX-101-02
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study of E6201 plus dabrafenib for the treatment of CNS metastases in BRAF V600-mutated metastatic melanoma. A total of up to N=28-34 subjects with melanoma metastasized to the CNS will be included.

Conditions

Malignant Melanoma; Brain Metastases

Keywords

Melanoma; CNS metastases; BRAF V600 mutation; E6201; Dabrafenib

Outcome Measures

Primary Outcomes (2)

• Intracranial Disease Overall Response Rate by RANO-BM

  CNS disease response will be assessed by Response Assessment in Neuro-Oncology - Brain Metastases (RANO-BM)

  At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.

• Intracranial Disease Overall Response Rate by RECIST 1.1

  CNS disease response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.

Secondary Outcomes (4)

• Intracranial Disease Duration of Response

  At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.

• Systemic Disease Overall Response Rate (Other Than in the CNS)

  At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.

• Progression-Free Survival

  From Cycle 1 Day 1 through 6 months following the last dose of study drug (each cycle is 28 days) up to 1 year.

• Overall Survival

  From Cycle 1 Day 1 through 6 months following the last dose of study drug or death, whichever is earlier (each cycle is 28 days) up to 1 year.

Study Arms (3)

Monotherapy Safety Run-in: E6201

EXPERIMENTAL

E6201 320 mg/m\^2 administered IV over 2 hours twice weekly on Days 1, 4, 8, 11, 15 and 18, repeated every 28 days (=1 cycle). Dose reductions for toxicity are 240 mg/m\^2 (Dose Level -1) and 160 mg/m\^2 (Dose Level -2) twice weekly.

Drug: E6201

Combination Safety Run-in: E6201 Plus Dabrafenib

EXPERIMENTAL

Dose Level 1: E6201 320 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -1: E6201 240 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -2: E6201 240 mg/m\^2 twice weekly plus dabrafenib 100 mg BID. Dose Level -3: E6201 160 mg/m\^2 twice weekly plus dabrafenib 100 mg BID Dose Level -4: E6201 160 mg/m\^2 twice weekly plus dabrafenib 75 mg BID. Dose Level -5: E6201 160 mg/m\^2 twice weekly plus dabrafenib 50 mg BID.

Drug: E6201 plus dabrafenib

Expansion: E6201 Plus Dabrafenib

EXPERIMENTAL

A total of up to N=18 will be treated at the E6201 plus dabrafenib combined MTD.

Drug: E6201 plus dabrafenib

Interventions

E6201 DRUG

E6201 formulated in cyclodextrin for IV administration.

Monotherapy Safety Run-in: E6201

E6201 plus dabrafenib DRUG

E6201 formulated in cyclodextrin for IV administration. Dabrafenib capsules for oral administration.

Combination Safety Run-in: E6201 Plus Dabrafenib; Expansion: E6201 Plus Dabrafenib

Eligibility Criteria

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

You may qualify if:

• Males and females ≥ 18 years of age
• Histologically or cytologically confirmed BRAFV600-mutated melanoma
• Documented metastasis of the primary tumor to the CNS
• BRAF-mutation melanoma tumor status will be established prior to entry based on previous BRAF-gene analysis or MEK pathway mutation reports from a CLIA qualified laboratory. If a report is not available, the mutation analysis will be performed at Screening on archival tissue
• Other metastatic melanoma systemic disease allowed
• At least one measurable brain metastasis, 0.5 - 3.0 cm, as assessed by MRI ≤ 3 weeks prior to initiation of study treatment, provided neurological sequelae have resolved completely and at least one measurable metastasis with documented disease progression is present on MRI
• Prior stereotactic radiosurgery and/or excision of up to 3 brain metastases is allowed \> 3 weeks before initiation of study treatment, provided neurological sequelae have resolved completely and at least one measurable metastasis with documented disease progression is present on MRI
• One prior line of immunotherapy for metastatic disease is allowed, if ≥ 2 weeks has elapsed between the end of therapy and initiation of study treatment
• Prior melanoma adjuvant immunotherapy is allowed, if ≥ 6 months has elapsed between the end of therapy and initiation of study treatment
• Prior melanoma adjuvant BRAF/MEK inhibitor therapy is allowed, if ≥ 12 months has elapsed between the end of therapy and initiation of study treatment
• Able to swallow and retain oral medication with no clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels (Combination Safety Run-in and Expansion Phases of the study only)
• Asymptomatic or symptomatic CNS metastasis is allowed
• Stable dose of corticosteroids for CNS metastasis for ≥ 7 days allowed
• Patients with seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for ≥ 14 days
• Bisphosphonates and/or denosumab are allowed

You may not qualify if:

• Urgent need of treatment to prevent acute neurologic deterioration, including urgent neurosurgery or radiotherapy
• Symptoms of uncontrolled intracranial pressure
• Symptomatic or untreated spinal cord compression
• Prior treatment with any chemotherapeutic or investigational agent
• Prior treatment with any BRAF and/or MEK inhibitor for metastatic disease
• Prior treatment with \> 1 line of immunotherapy for metastatic disease
• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV
• QT interval corrected for rate (QTc) \> 480 msec for on the ECG obtained at Screening using Fridericia method for QTc calculation
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring systemic antiviral treatment within the last week prior to study treatment
• Other active infection requiring IV antibiotic usage within the last week prior to study treatment
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
• Pregnant or breast-feeding

Sponsors & Collaborators

• Spirita Oncology, LLC: lead
• University of Arizona: collaborator

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione; dabrafenib

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

Limitations and Caveats

Due to the departure of the study PI from the institution, the study was terminated early.

Results Point of Contact

• Title: Chief Development Officer
• Organization: Spirita Oncology, LLC

linda.paradiso@spiritaoncology.com

+1 (713) 898-8965

Study Officials

• Hani M Babiker, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4 subjects were treated in the E6201 Monotherapy Safety Run-in Phase. A total of 6-12 subjects are anticipated in the E6201 plus dabrafenib Combination Safety Run-in Phase. Once an MTD of the combination is determined, a total of 6 subjects will be treated at the combined MTD before the Expansion Phase will begin. In the Expansion Phase, an additional cohort of up to N=18 subjects will be treated at the combined E6201 plus dabrafenib MTD. Subjects treated at the MTD in the Combination Safety Run-in Phase will count towards accrual in the Expansion Phase.

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: July 2, 2018
• Primary Completion: April 30, 2021
• Study Completion: October 11, 2021
• Last Updated: May 20, 2022
• Results First Posted: May 20, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)