E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
GSK1120212 is currently being developed for a number of solid tumors, including metastatic BRAF-mutant melanoma (Phase 3), pancreatic cancer (Phase 2) and non small cell lung cancer (Phase 2), and in hematological malignancies, including acute-myeloid leukemia (AML) or chronic myelo-monocytic leukemia (CMML). |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To estimate the relative bioavailability of 2mg GSK1120212 pediatric oral solution formulation to 2mg of the tablet formulation of GSK1120212 in fasted subjects. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of a single 2mg dose of the pediatric oral solution formulation of GSK1120212 following administration to fasted subjects.
To investigate the safety and tolerability of a single 2mg dose of the tablet formulation of GSK1120212 following administration to fasted subjects.
To characterize the PK of GSK1120212 after administration of the pediatric oral solution and tablet formulation in fasted subjects.
To investigate the palatability of the pediatric oral solution formulation of GSK1120212 following administration to fasted subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, 18 years of age or older, at the time of signing the informed consent.
2. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
3. Able to swallow and retain oral medication.
4. Histologically- or cytologically-confirmed diagnosis of a solid tumor malignancy that is not responsive to standard therapies; or for which there is no approved or curative therapy; or for subjects which refuse standard therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequate baseline organ function as defined in Table 4 in the protocol.
7. Women of child-bearing potential must have a negative serum pregnancy test within 14 days of first dose of investigational product administration and agree to use effective contraception, as defined in Section 7.1.1 of the protocol, during the study and for 6 weeks following the last dose of investigational product.
8. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.1 of the protocol. This criterion must be followed from the time of the first dose of study medication until 16 weeks after
the last dose of GSK1120212. |
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E.4 | Principal exclusion criteria |
1. Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within 3 weeks prior to randomization; chemotherapy regimens without delayed toxicity within 2 weeks prior to randomization; or use of an investigational anticancer drug within 4 weeks prior to randomization.
2. Unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0 [NCI-CTCAE, 2009]) from previous anti-cancer therapy except Grade 2 decreased haemoglobin levels or alopecia.
3. Pre-existing peripheral neuropathy ≥ Grade 2.
4. Has participated in a clinical trial and received investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product, whichever is longer, prior to the first dose of investigational product in this study.
5. Has participated in a clinical trial that resulted in or made a donation of blood or blood products in excess of 500mL within 56 days of the first dose of investigational product in this study.
6. Has presence of active GI disease or other condition (e.g., gastrectomy, bariatric surgery, small or large bowel resection, or cholecystectomy) that may interfere significantly with absorption of drugs.
7. 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 with the study procedures, in the opinion of the investigator or the GSK medical monitor.
8. History of interstitial lung disease or pneumonitis.
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 hypertension, uncontrolled systemic disease(s) 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
• Intraocular pressure > 21mm Hg
10. Has symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
NOTE: 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 are not currently taking corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to Day 1 of the study are permitted. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs (EIAEDs).
11. QTcB or QTcF ≥480msec.
12. Subject has a history or evidence of cardiovascular risk, including any of the following:
• History or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with controlled atrial fibrillation for >30days prior to randomization are eligible.
• History of acute coronary syndromes, including myocardial infarction and unstable angina, coronary angioplasty, or stenting, within 6months prior to randomization.
13. History or evidence of current ≥Class II congestive heart failure as defined by New York Heart Association (NYHA; Appendix 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary PK endpoints will be AUC(0-∞), AUC(0-t), and Cmax of GSK1120212. Secondary PK endpoints will be tmax and
t1/2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK endpoints will be evaluated based on blood draws done from day 1 through day 7 of each of the two dosing periods. |
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E.5.2 | Secondary end point(s) |
Safety and tolerability will be assessed by physical examinations, measurement of blood pressure, heart rate, laboratory safety
screens and assessment of adverse events and serious adverse events. The secondary PK endpoint will be AUC(0-24), half-life and Tmax of GSK1120212.
Bitterness, sweetness, overall taste and aroma will each be ranked by subjects on a 4-point scale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety will be monitored from start of study dosing through to the last followup visit. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Yes |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Please note that there is no controlled/comparator in this study. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Please note that there is no controlled/comparator in this study. |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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
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The end of the study is defined as the last subject's last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 20 |