Clinical trial NCT01231581: Study of GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Metastatic Pancreatic Cancer
Official title: A Randomized, Double-Blind Placebo-Controlled Phase II Study of the MEK Inhibitor GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Subjects With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-11-01
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization until death due to any cause or until the data cutoff of 15-March-2013 (up to 24 months)
Secondary outcomes:
measure: Progression-free Survival (PFS) as Assessed by the Investigator
timeFrame: From randomization until disease progression (PD) or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months)
measure: Number of Participants With an Investigator-assessed Best Response, With or Without Confirmation, of Complete Response (CR) or Partial Response (PR)
timeFrame: From randomization until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months)
measure: Investigator-Assessed Duration of Response
timeFrame: From the first documented CR or PR until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 13 months)
measure: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)
timeFrame: From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 15-March-2013 (up to 21 months)
measure: Number of Participants (Par.) With a Worst-case Change to Grade 3 or Grade 4 From Baseline Grade in Chemistry Parameters
timeFrame: From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months)
measure: Number of Participants With Change From Baseline Increase to Grade 3/Grade 4 in Lab Hematology Test Measurements
timeFrame: From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Gueishan Township,Taoyuan County
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Infante JR, Somer BG, Park JO, Li CP, Scheulen ME, Kasubhai SM, Oh DY, Liu Y, Redhu S, Steplewski K, Le N. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. Eur J Cancer. 2014 Aug;50(12):2072-81. doi: 10.1016/j.ejca.2014.04.024. Epub 2014 Jun 7.