Clinical Trials /

A Clinical Trial of Patients With Melanoma



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.

Related Conditions:
  • Melanoma
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: A Clinical Trial of Patients With Melanoma
  • Official Title: A Phase 1B Clinical Trial of Dabrafenib, Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Clinical Trial IDs

  • ORG STUDY ID: STU 102015-074
  • NCT ID: NCT02915666


  • Melanoma


Digoxin CombinationLanoxinDigoxin combination for Melanoma
DabrafenibTafinlarDigoxin combination for Melanoma
TrametinibMekinistDigoxin combination for Melanoma


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.

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.

Trial Arms

Digoxin combination for MelanomaExperimentalDrugs: Dabrafenib 150mg PO 2x daily, Trametinib 2 mg PO daily, and Digoxin 0.25 mg PO daily for 8-week cycles.
  • Digoxin Combination
  • Dabrafenib
  • Trametinib

Eligibility Criteria

        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

          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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of DLTs
Time Frame:Every 3 weeks for 36 months
Safety Issue:
Description: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


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:University of Texas Southwestern Medical Center

Trial Keywords

  • Melanoma, skin

Last Updated

May 15, 2018