Study of GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Metastatic Pancreatic Cancer
Condition: Cancer
Intervention: GSK1120212; Gemcitabine; Placebo
Intervention description: administered orally starting on day 1 followed by a continuous daily dosing of 2.0 mg; Intravenous gemcitabine infused over 30 minutes weekly for 7 weeks followed by one week of rest from treatment. Subsequent cycles will consist of 1000 mg/m2 intravenous infusion over 30 minutes on days 1, 8, and 15 followed by 1 week of rest from treatment for each 28-day treatment period.; administered orally starting on day 1 followed by a continuous daily dosing of 2.0 mg
Intervention MeSH terms: Gemcitabine; Trametinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      GSK1120212 is a potent and highly selective inhibitor of MEK phosphorylation and kinase
      activity and has demonstrated potent anti-proliferative activity against human pancreatic
      cancer cell lines. This study is a Phase II, randomized placebo-controlled trial of the MEK
      inhibitor GSK1120212 plus gemcitabine vs. placebo plus gemcitabine in subjects with
      metastatic pancreatic cancer. Eligible subjects will receive intravenous gemcitabine with
      oral GSK1120212 or placebo. Therapy will continue until treatment discontinuation criteria
      are met. The primary objective will be to compare the overall survival of subjects in the
      GSK1120212 plus gemcitabine arm vs. subjects in the placebo plus gemcitabine arm. Secondary
      objectives include comparison of progression free survival, overall response rate, and
      duration of response between the two arms. Exploratory research objectives include the
      evaluation of population pharmacokinetics as well as blood and tissue based biomarkers.
      Safety will also be monitored throughout dosing.

      Once the determined number of survival events has occurred, if subjects are eligible, they
      will have the option to enter MEK114375, an open-label, Phase Ib rollover study of GSK1120212
      monotherapy or GSK1120212 in combination with other anti-cancer treatments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years old or older

          -  Histologically or cytologically confirmed diagnosis of metastatic (Stage IV)
             adenocarcinoma of the pancreas with measurable or non-measurable disease per Response
             Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group
             (ECOG) scale

          -  All prior treatment related toxicities must be Common Terminology Criteria for Adverse
             Events (CTCAE) (Version 4.0) ≤ Grade 1 (except alopecia) at the time of randomization

          -  Adequate baseline organ function

          -  Able to swallow and retain orally administered medication and does not have any
             clinically significant gastrointestinal abnormalities that may alter absorption such
             as malabsorption syndrome or major resection of the stomach or bowels

        Exclusion Criteria:

          -  Prior systemic therapy (i.e., chemotherapy, immunotherapy, hormone therapy, , targeted
             therapy or any investigational anti-cancer drug) for metastatic pancreatic
             adenocarcinoma.

        (Prior treatment with 5-FU based or gemcitabine administered as a radiation sensitizer
        during and up to 4 weeks after radiation therapy is allowed. Prior systemic chemotherapy in
        the adjuvant setting is allowed ; however, prior therapy with gemcitabine is allowed only
        if tumor recurrence occurred at least 6 months after completing the last dose of
        gemcitabine)

          -  History of another malignancy. Exception: 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. Subjects with second malignancies
             that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor
             if unsure whether second malignancies meet requirements specified above

          -  Any serious and/or unstable pre-existing medical (aside from malignancy exception
             above), psychiatric disorder, or other conditions that could interfere with subject's
             safety, obtaining informed consent or compliance to the study procedures, in the
             opinion of the Investigator or GSK Medical Monitor

          -  History of interstitial lung disease or pneumonitis

          -  History or current evidence / risk of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR)

          -  Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression

          -  History of acute coronary syndromes (including unstable angina), coronary angioplasty,
             or stenting within the past 6 months