Overview

Study of GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Metastatic Pancreatic Cancer

Status:
Completed
Trial end date:
2013-02-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
GlaxoSmithKline
Treatments:
Gemcitabine
Trametinib
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