Melanoma
Conditions
Keywords
Melanoma, skin
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.
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.
Interventions
DRUGDigoxin Combination
Digoxin 0.25 mg PO daily will be given for 8-week cycles
DRUGDabrafenib
dabrafenib 150mg PO twice daily for 8-week cycles
DRUGTrametinib
trametinib 2 mg PO daily for 8-week cycles
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of DLTs | 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 |
Countries
United States
Outcome results
None listed