A Phase 1B Clinical Trial of Dabrafenib, Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Overview
- Phase
- Phase 1
- Status
- Withdrawn
- Locations
- 1
- Primary Endpoint
- Frequency of DLTs
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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-
- •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.
- •Exclusion Criteria
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Digoxin Combination (Drug)
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.
Intervention: Dabrafenib (Drug)
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.
Intervention: Trametinib (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
No secondary outcomes reported