A Clinical Trial of Patients With Melanoma

NCT02915666 | Withdrawn Phase 1 DMC

• 1 other identifier: STU 102015-074
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to find out if the combination of dabrafenib, trametinib and digoxin will lessen the side effects that you may experience and to measure your response and duration of response to the combination of drugs.

Conditions

Melanoma

Keywords

Melanoma, skin

Outcome Measures

Primary Outcomes (1)

• Frequency of DLTs

  DLTs will be defined based on the rate of drug-related grade 3-4 toxicities that do not resolve within 3 weeks or any toxicities requiring permanent discontinuation of any of the study drugs

  Every 3 weeks for 36 months

Study Arms (1)

Digoxin combination for Melanoma

EXPERIMENTAL

Drugs: Dabrafenib 150mg PO 2x daily, Trametinib 2 mg PO daily, and Digoxin 0.25 mg PO daily for 8-week cycles.

Drug: Digoxin Combination; Drug: Dabrafenib; Drug: Trametinib

Interventions

Digoxin Combination DRUG

Digoxin 0.25 mg PO daily will be given for 8-week cycles

Also known as: Lanoxin

Digoxin combination for Melanoma

Dabrafenib DRUG

dabrafenib 150mg PO twice daily for 8-week cycles

Also known as: Tafinlar

Digoxin combination for Melanoma

Trametinib DRUG

trametinib 2 mg PO daily for 8-week cycles

Also known as: Mekinist

Digoxin combination for Melanoma

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of unresectable or metastatic BRAF V600 mutant melanoma.
• Age \> 18 years.
• Naïve or any number of prior systemic therapeutic regimens for unresectable stage III or stage IV melanoma, except prior BRAF or MEK inhibitor agents. This includes chemotherapy, immunotherapy, biochemotherapy, or investigational treatments. Patients may also have received therapies in the adjuvant setting.
• Performance status ECOG 0-2.
• Adequate organ function as defined below:
• A.- total bilirubin 3 x institutional upper limit of normal B.- AST(SGOT)/ALT(SPGT) ≤ 5 X institutional upper limit of normal C.- creatinine 3 mg/dL D.- cardiac ejection fraction \> 50% E.- QTcF ≤ 480msec F.-PT/INR/aPTT ≤ 1.5 x institutional upper limit of normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• All sites of disease must be evaluated within 4 weeks prior to beginning therapy. Patients must have measurable disease as defined by RECIST v1.1 (see Section 6).
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Subjects who have had chemotherapy or radiotherapy or any systemic therapy for melanoma within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. No concomitant therapy is allowed including IL2, interferon, ipilimumab, anti-PD-1 or anti-PD-L1 antibody, cytotoxic chemotherapy, immunosuppressive agents, or other investigational therapies.
• Active infection with hepatitis B or C or HIV.
• Subjects with active CNS disease are excluded. Patient with brain metastases previously treated with surgery or radiation therapy and with confirmed SD for \>2 weeks are allowed.
• Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
• History of predisposition to retinal vein occlusion or central serous retinopathy.
• Prior BRAF or MEK inhibitor therapy.
• Wolff-Parkinson White syndrome or the presence of an intra-cardiac defibrillator (see Section 7.2.1).
• Known cardiac metastases.
• History of interstitial lung disease or unresolved pneumonitis.
• Immediate or delayed hypersensitivity to digoxin.
• Patients requiring concomitant medications listed in section 4.3 that are not able to be switched to a reasonable alternative.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75063, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

digoxin, nicotinic acid, pentifylline drug combination; Digoxin; dabrafenib; 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)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Arthur Frankel, MD

  UT Southwestern.edu

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: September 27, 2016
• Study Start: October 1, 2016
• Primary Completion: July 17, 2017
• Study Completion: July 17, 2017
• Last Updated: May 15, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)