| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic pancreatic cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Metastatic pancreatic cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033605 |
| E.1.2 | Term | Pancreatic cancer metastatic |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective is to compare overall survival (OS) of subjects treated with GSK1120212 plus gemcitabine to those treated with placebo plus gemcitabine.
The primary efficacy endpoint is presented in Section 7.2.1.1 of the Protocol. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives are:
•To compare the progression free survival (PFS) of subjects treated with GSK1120212 plus gemcitabine to those
treated with placebo plus gemcitabine.
•To compare the overall response rate (ORR) of subjects treated with GSK1120212 plus gemcitabine to those
treated with placebo plus gemcitabine.
•To compare the duration of response of subjects treated with GSK1120212 plus gemcitabine to those treated with
placebo plus gemcitabine.
The secondary efficacy endpoints are presented in Section 7.2.1.2 of the Protocol. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 7.2.7 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.
|
|
| E.4 | Principal 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 congestive heart failure as defined by New York Heart Association (NYHA; Appendix 4).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of the study is OS, defined as the time from randomization until death due to any cause. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| One interim and one final analysis |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints of this study are:
- PFS: defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause.
- ORR: defined as the percentage of subjects with a CR or PR as per RECIST 1.1 criteria.
- Duration of Response: defined, for the subset of subjects with a CR or PR, as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Korea, Republic of |
| Taiwan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Once approximately 80% of the total number of randomized subjects haves died or are otherwise lost to follow-up, the study will be closed. Subjects who are experiencing therapeutic benefit from treatment and an acceptable tolerability profile with either GSK1120212 as monotherapy or as part of a combination regimen with gemcitabine, will have the option to transition to MEK114375, a rollover study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
