Cancer
Conditions
Brief summary
This was an open-label study to permit subjects with solid tumors or leukemia, who were clinically benefitting on another GSK sponsored trial with GSK1120212 either monotherapy or in combination continued access to GSK1120212.
Interventions
DRUGGSK1120212
up to 2 mg/day
DRUGDocetaxel + GSK1120212
dose as defined in the dose escalation protocol.
DRUGErlotinib + GSK1120212
dose as defined in the dose escalation protocol.
DRUGPemetrexed + GSK1120212
dose as defined in the dose escalation protocol
DRUGCarboplatin + GSK1120212
dose as defined in the dose escalation protocol
DRUGNab-paclitaxel + GSK1120212
dose as defined in the dose escalation protocol
DRUGGemcitabine + GSK1120212
dose as defined in the dose escalation protocol
DRUGEverolimus + GSK1120212
dose as defined in the dose escalation protocol
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has provided signed informed consent for this study. 2. Has demonstrated compliance during the parent study with study treatment(s), treatment visit schedules, and the requirements and restrictions listed in the consent form. 3. Is currently participating in GSK1120212 study and is receiving treatment with GSK1120212. 4. Is currently receiving clinical benefit as determined by the investigator from previous treatment with GSK1120212 either as monotherapy or as part of a combination treatment regimen. 5. Continued ability to swallow and retain orally administered study treatment(s) and does not have any clinically significant GI abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. 6. Female subjects of childbearing potential, as defined in the parent study, must be willing to continue practicing the same acceptable method of contraception as used in the parent study during the rollover study and for at least 4 months after the last dose of GSK1120212. 7. Female subjects of childbearing potential, as defined in parent study, must have negative serum pregnancy tests at the time of transition to this study. 8. Subjects enrolled in France: 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.
Exclusion criteria
1. Permanent discontinuation of GSK1120212 in the parent study due to toxicity or disease progression. 2. Current use of a prohibitive medication(s) as listed in Section 6.2. NOTE: Use of anticoagulants such as warfarin is permitted; however, the international normalization ratio (INR) must be monitored in accordance with local institutional practice. 3. Any unresolved toxicity that meets the study treatment discontinuation or study withdrawal criteria from the parent study at the time of transition to this study. 4. Bazett-corrected QT (QTcB) interval ≥501 msec at the time of transition to this study 5. Left ventricular ejection fraction (LVEF) \< institutional lower limit of normal (LLN) by ECHO (preferred) or MUGA scan at the time of transition to this study. 6. Nursing female. 7. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions at the time of transition to this study 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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Until 30 days after the last dose of study treatment. Subjects may have continued to receive study treatment until disease progression, death, unacceptable toxicity or until locally commercially available. The maximum duration of exposure was 76 months. | Number of participants with adverse events as a measure of safety and tolerability |
Countries
Canada, France, Netherlands, South Korea, Taiwan, United States
Participant flow
Recruitment details
159 subjects received treatment with GSK1120212 and were included in the safety set.
Pre-assignment details
Continued treatment with GSK1120212 was provided for subjects who had previously participated in a GSK1120212 study and who continued to receive clinical benefit as well as have an acceptable safety profile with GSK1120212.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (GSK1120212 < 24 Weeks) Subjects on GSK1120212 Monotherapy and have been treated less than 24 weeks in their parent study. | 126 |
| Cohort B (GSK1120212 >= 24 Weeks) Subjects on GSK monotherapy who have been treated for 24 weeks or greater in their parent study. Also, subjects entering this study from any GSK1120212 combo trial. | 33 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 26 | 7 |
| Overall Study | Study closed/terminated | 1 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 2 |
Baseline characteristics
| Characteristic | Cohort B (GSK1120212 >= 24 Weeks) | Total | Cohort A (GSK1120212 < 24 Weeks) |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 11.3 | 61.2 years STANDARD_DEVIATION 12.1 | 61.0 years STANDARD_DEVIATION 12.34 |
| Race/Ethnicity, Customized Asian | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 9 Participants | 6 Participants |
| Race/Ethnicity, Customized Native American/Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 144 Participants | 116 Participants |
| Sex: Female, Male Female | 17 Participants | 83 Participants | 66 Participants |
| Sex: Female, Male Male | 16 Participants | 76 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 126 | 3 / 33 |
| other Total, other adverse events | 115 / 126 | 28 / 33 |
| serious Total, serious adverse events | 26 / 126 | 13 / 33 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Until 30 days after the last dose of study treatment. Subjects may have continued to receive study treatment until disease progression, death, unacceptable toxicity or until locally commercially available. The maximum duration of exposure was 76 months.
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A (GSK1120212 < 24 Weeks) | Number of Participants With Adverse Events | Treatment-Related Adverse Events | 101 Participants |
| Cohort A (GSK1120212 < 24 Weeks) | Number of Participants With Adverse Events | Adverse Events | 119 Participants |
| Cohort A (GSK1120212 < 24 Weeks) | Number of Participants With Adverse Events | Serious Adverse Events | 26 Participants |
| Cohort A (GSK1120212 < 24 Weeks) | Number of Participants With Adverse Events | Treatment-Related Serious Adverse Events | 8 Participants |
| Cohort B (GSK1120212 >= 24 Weeks) | Number of Participants With Adverse Events | Treatment-Related Serious Adverse Events | 4 Participants |
| Cohort B (GSK1120212 >= 24 Weeks) | Number of Participants With Adverse Events | Treatment-Related Adverse Events | 26 Participants |
| Cohort B (GSK1120212 >= 24 Weeks) | Number of Participants With Adverse Events | Serious Adverse Events | 13 Participants |
| Cohort B (GSK1120212 >= 24 Weeks) | Number of Participants With Adverse Events | Adverse Events | 30 Participants |