Japan PhI/II of GSK2118436 and GSK1120212 Combination in Subjects With BRAF V600E/K Mutation Positive Advanced Solid Tumors (Phase I Part) or Cutaneous Melanoma (Phase II Part)
Condition: Solid Tumours
MeSH terms: Melanoma
Intervention: dabrafenib; trametinib
Intervention description: 150 mg twice daily; 2 mg once daily
Intervention MeSH terms: Trametinib; Dabrafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Advanced solid tumors; BRAF; Melanoma

Summary:

      This is a Japanese Phase I/II, open-label, non-controlled study to evaluate the safety,
      tolerability, pharmacokinetic profile, and efficacy of the combination of GSK2118436 and
      GSK1120212 in subjects with BRAF V600E/K mutation positive advanced solid tumors (Phase I
      part) and BRAF V600E/K mutation positive cutaneous melanoma (Phase II part).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Capable of given written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Male or female age 20 years or greater; able to swallow and retain oral medication.

          -  BRAF mutation positive advanced solid tumor ( Phase I part). BRAF mutation positive
             melanoma (Phase II part).

          -  Measurable disease according to RECIST version 1.1.

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

          -  Agree to contraception requirements.

          -  Adequate organ system function.

        Exclusion Criteria:

          -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or
             biologic therapy).

          -  Phase II part ONLY: Prior systemic anti-cancer treatment (chemotherapy, immunotherapy,
             biologic therapy, vaccine therapy, or investigational treatment) for Stage IIIC
             (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the
             adjuvant setting is allowed.

          -  Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity,
             biologic therapy, or immunotherapy within 28 days prior to the study treatment (6
             weeks for prior nitrosourea or mitomycin C), or daily or weekly chemotherapy without
             the potential for delayed toxicity within 14 days prior to the study treatment.
             Limited radiotherapy within the last 2 weeks. (Note: Ipilimumab treatment must end at
             least 8 weeks prior to the study treatment.)

          -  Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days),
             whichever is shorter, prior to the study treatment.

          -  Current use of a prohibited medication or requires any of these medications during
             treatment with the study drugs.

          -  A history of another malignancy. Subjects who have been disease-free for 5 years, or
             subjects with a history of completely resected non-melanoma skin cancer, or
             successfully treated in situ carcinoma are eligible.

          -  Any serious or unstable pre-existing medical conditions (aside from malignancy
             exceptions specified above), psychiatric disorders, or other conditions that could
             interfere with the subject's safety, obtaining informed consent, or compliance with
             study procedures (e.g., uncontrolled diabetes).

          -  Presence of active gastrointestinal disease or other condition that will interfere
             significantly with the absorption, distribution, metabolism, or excretion of drugs.

          -  History of pneumonitis or interstitial lung disease.

          -  Known HIV infection.

          -  Certain cardiac abnormality

          -  A history or current evidence/risk of retinal vein occlusion or central serous
             retinopathy.

          -  Pregnant or lactating female.