Dabrafenib and Trametinib With Radiosurgery in Melanoma Brain Mets

NCT01721603 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 12857
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and find out what effects, good and/or bad, dabrafenib (a BRAF inhibitor) alone or dabrafenib when given in combination with gamma knife radiosurgery has on participants with a certain type of skin cancer (BRAFV600E melanoma) and brain metastases (tumors that have spread to the brain).

Conditions

BRAFV600E Melanoma Patients

Keywords

BRAFV600E melanoma patients; melanoma; stereotactic radiosurgery; BRAFV600E melanoma brain metastases; dabrafenib; SRS

Outcome Measures

Primary Outcomes (1)

• Patients Reaching 6 Month Distant Brain Metastasis-free Survival (DBMFS)

  Determine whether dabrafenib combined with stereotactic radiosurgery (SRS) and trametinib improves the 6 month DBMFS rate of BRAFV600E melanoma patients for whom the standard of care is stereotactic radiosurgery (≤4 brain lesions and no lesion \> 3 cm) in comparison with similar historical controls treated with radiosurgery alone.

  Up to 6 months after surgery

Secondary Outcomes (7)

• Patients Displaying 6-month Local Control Rate

  From surgery up to 6 months

• Best Overall Response Rate (by RECIST v1.1 )

  From surgery up to 12 months

• Median Duration of Freedom From New Brain Metastases( by RECIST v1.1 )

  From surgery up to 12 months

• Median Time to Progression

  From surgery up to 12 months

• Systemic Overall Response Rate

  From surgery up to 12 months

Study Arms (1)

Dabrafenib + Trametinib + gamma knife radiosurgery

EXPERIMENTAL

Drug: Dabrafenib; Procedure: Gamma Knife Radiosurgery; Drug: Trametinib

Interventions

Dabrafenib DRUG

150 mg capsule by mouth twice daily

Also known as: GSK2118436

Dabrafenib + Trametinib + gamma knife radiosurgery

Gamma Knife Radiosurgery PROCEDURE

This will be delivered using Gamma Knife technology. Patients will be fitted with a stereotactic head-frame for stereotactic localization of brain metastases.

Also known as: SRS, Stereotactic Radiosurgery

Dabrafenib + Trametinib + gamma knife radiosurgery

Trametinib DRUG

2 mg by mouth once daily from beginning at Cycle 3 Day 1, until progression of disease, withdrawal of consent, or the development of intolerable treatment associated toxicity.

Also known as: GSK1120212

Dabrafenib + Trametinib + gamma knife radiosurgery

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed BRAFV600E melanoma
• ECOG PS 0-2
• days elapsed from last treatment with surgery.
• At least 28 days or five half-lives (whichever is longer) have elapsed from last dose of any approved or investigational therapy for metastatic melanoma.
• Appropriate birth control for men and women with childbearing potential
• Corticosteroid dose stable for at least 14 days
• Adequate end-organ function:
• ANC ≥ 1.5x109/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥100 x109/L
• Total bilirubin ≤ 1.5x ULN
• AST and ALT ≤ 2.5x ULN
• Creatinine ≤ 1.5 mg/dL
• PT/PTT ≤ 1.5x ULN
• LVEF ≥ 50%

You may not qualify if:

• Neurological symptoms from melanoma brain metastases
• Patients may not have received prior therapy with dabrafenib, vemurafenib, or other potent, highly effective BRAF inhibitors. Prior therapy with sorafenib is permitted.
• Any indication for urgent or emergent neurosurgery. Patient may enroll after neurosurgery at least 14 days after neurosurgery as long as they meet all other study qualifications.
• Pregnant or lactating women. The effects of dabrafenib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use a highly effective method of contraception including: hormonal contraceptives (oral contraceptives, Nuvaring, Depo Provera) an intrauterine device, true abstinence or two barrier methods of birth control including condoms with cervical cap or diaphragm. Baseline pregnancy testing is required for all women of child-bearing potential. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol who are sexually active with women of child bearing potential must also agree to use adequate contraception prior to and during the study as outlined above, and for, and four months after completion of study drug administration.
• History of known cardiac arrhythmias or acute coronary syndromes within the past 24 weeks.
• History of a second malignancy with evidence of active disease within the past 3 years except non-melanoma skin cancer, indolent prostate cancer, and stable CLL without lymphadenopathy
• Complete resection of a single brain metastasis or of all known brain metastases. Patients who have undergone subtotal resection are eligible providing residual disease is \< 2.0 cm in maximum diameter.
• Patients with metastases within 2 mm of the optic nerve or optic chiasm so that some portion of the optic nerve or chiasm would receive \> 9 Gy from radiosurgery.
• Patients with metastases in the brainstem.
• Contraindication to MRI (such as cardiac pacemaker).
• The following medications or non-drug therapies are prohibited:
• Other anti-cancer therapy while on treatment in this study.
• Use of other investigational drugs within 28 days preceding the first dose of dabrafenib.
• Antiretroviral drugs. Subjects with known HIV are ineligible for study participation.
• Herbal remedies (i.e., St. John's wort).

Sponsors & Collaborators

• University of California, San Francisco: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of San Francisco, California

San Francisco, California, 94115, United States

Location

Related Publications (1)

• Patel KR, Chowdhary M, Switchenko JM, Kudchadkar R, Lawson DH, Cassidy RJ, Prabhu RS, Khan MK. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res. 2016 Aug;26(4):387-94. doi: 10.1097/CMR.0000000000000268.

  PMID: 27223498 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; Radiosurgery; trametinib

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Alain Algazi, MD
• Organization: University of California, San Francisco

Alain.Algazi@ucsf.edu

(415) 353-7552

Study Officials

• Alain Algazi, MD

  University of California, San Francisco

  STUDY CHAIR

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: Assistant Clinical Professor

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 6, 2012
• Study Start: April 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2017-12

Locations

US (1)