Phase 2
N=160
Study of GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Metastatic Pancreatic Cancer
Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01231581 ↗Enrolled (actual)
160
Serious AEs
49.4%
Results posted
Sep 2013
Primary outcome: Primary: Overall Survival — 8.4; 6.7 months — p=0.352
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK1120212 (Drug); Gemcitabine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Apr 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
8.4; 6.7 | 0.352 |
| SECONDARY Progression-free Survival (PFS) as Assessed by the Investigator |
16.1; 15.1 | — |
| SECONDARY Number of Participants With an Investigator-assessed Best Response, With or Without Confirmation, of Complete Response (CR) or Partial Response (PR) |
1; 0; 16; 14 | — |
| SECONDARY Investigator-Assessed Duration of Response |
23.9; 16.1 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) |
80; 80; 42; 37 | — |
| SECONDARY Number of Participants (Par.) With a Worst-case Change to Grade 3 or Grade 4 From Baseline Grade in Chemistry Parameters |
7; 4; 0; 0; 7; 4 | — |
| SECONDARY Number of Participants With Change From Baseline Increase to Grade 3/Grade 4 in Lab Hematology Test Measurements |
3; 0; 0; 0; 24; 13 | — |
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
Data sourced from ClinicalTrials.gov (NCT01231581). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.