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

Phase 1

Conditions: Metastatic pancreatic cancer
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 14.0Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2010-019578-34-BE

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Signed written informed consent
2. Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the pancreas with measurable or non-measurable disease per RECIST 1.1.
3. Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale [Oken, 1982] (see Appendix 4).
4. All prior treatment related toxicities must be CTCAE (Version 4.0) = Grade 1 (except alopecia) at the time of randomization.
5. Adequate baseline organ function defined in Table 5 (please refer to pae 28 of the Protocol).
6. 18 years old or older.
7. Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception, as defined in Section 7.3.7, during the study and for 30 days following the last dose of study drug.
and
Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 7.3.7 starting 14 days prior to the first dose of study medication until 16 weeks after the last dose of study medication.
8. 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.
Subjects with prior Whipple procedure are eligible for this study.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Lactating female.
2. History of another malignancy.
Exception: Subjects who have been disease-free for 3 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.
3. 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.
4. 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 neoadjuvant or 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
5. History of interstitial lung disease or pneumonitis.
6. Radiotherapy completed within 2 weeks prior to randomization.
• Definitive radiotherapy to areas other than the thoracic region affecting lungs is allowed if completed at least 4 weeks prior to randomization and toxicities resolved per inclusion #4.
• Limited radiotherapy (for palliative care) to areas other than the thoracic region completed at least 2 weeks prior to randomization is allowed if toxicities resolved per inclusion #4.
7. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to dimethyl sulfoxide (DMSO).
8. Current use of a prohibited medication (see Section 6.2).
9. History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
• History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertention, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
• Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
• Evidence of new optic disc cupping
• Evidence of new visual field defects on automated perimetry
• Intraocular pressure > 21 mm Hg as measured by tonography

10. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
• Subjects previously treated for these conditions that have had stable central nervous system (CNS) disease (verified with consecutive imaging studies) for > 3 months, are asymptomatic and off corticosteroids or are on a stable dose of corticosteroids for at least 1 month prior to study Day 1 are eligible.
11. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 6 months.
12. QTcB = 480 msec.
13. History or evidence of clinically significant uncontrolled arrhythmias
• Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are eligible.
14. History or current evidence of = Class II conge