A Clinical Trial of Patients With Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02915666
Recruitment Status : Withdrawn (No subjects consented for enrollment on this study.)
First Posted : September 27, 2016
Last Update Posted : May 15, 2018
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Digoxin Combination Drug: Dabrafenib Drug: Trametinib Phase 1

Detailed Description:

Melanoma is a cancer of melanocytes--melanin pigment producing cells, and the cancer originates in the skin, uvea, acral tissues and mucosal tissues. Melanoma incidence and mortality are increasing in the U.S. with over 80,000 cases/year and 9,000 deaths/year. Advanced melanoma occurs either after treatment for localized melanoma or de novo and is associated with chemo-resistance and a median survival of 9 months.

The study is a prospective, single-arm, one-site therapeutic trial of the combination of Dabrafenib + Trametinib + Digoxin for advanced V600 mutant melanoma.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1B Clinical Trial of Dabrafenib, Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Actual Study Start Date : October 2016
Actual Primary Completion Date : July 17, 2017
Actual Study Completion Date : July 17, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Digoxin combination for Melanoma
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
Digoxin 0.25 mg PO daily will be given for 8-week cycles
Other Name: Lanoxin

Drug: Dabrafenib
dabrafenib 150mg PO twice daily for 8-week cycles
Other Name: Tafinlar

Drug: Trametinib
trametinib 2 mg PO daily for 8-week cycles
Other Name: Mekinist

Primary Outcome Measures :
  1. Frequency of DLTs [ Time Frame: Every 3 weeks for 36 months ]
    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologic diagnosis of unresectable or metastatic BRAF V600 mutant melanoma.
  2. Age > 18 years.
  3. 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.
  4. Performance status ECOG 0-2.
  5. 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

  6. 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).
  7. 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).
  8. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

  1. 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.
  2. Active infection with hepatitis B or C or HIV.
  3. 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.
  4. 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.
  5. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (>class II based on NYHA), unstable angina pectoris, clinically significant and uncontrolled cardiac arrhythmia, uncontrolled thyroid disease, or psychiatric illness/social situations that would limit compliance with study requirements. Acute coronary syndrome within 24 weeks. Note atrial fibrillation controlled >30 days is not an exclusion.
  6. History of predisposition to retinal vein occlusion or central serous retinopathy.
  7. Prior BRAF or MEK inhibitor therapy.
  8. Wolff-Parkinson White syndrome or the presence of an intra-cardiac defibrillator (see Section 7.2.1).
  9. Known cardiac metastases.
  10. History of interstitial lung disease or unresolved pneumonitis.
  11. Immediate or delayed hypersensitivity to digoxin.
  12. Patients requiring concomitant medications listed in section 4.3 that are not able to be switched to a reasonable alternative.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02915666

United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75063
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Principal Investigator: Arthur Frankel, MD UT

Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT02915666     History of Changes
Other Study ID Numbers: STU 102015-074
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Texas Southwestern Medical Center:
Melanoma, skin

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs