CancerPhase 1NCT01248858
Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK2126458 and GSK1120212 Combination Therapy in Subjects With Advanced Solid Tumors.
A Phase 1 study testing GSK2126458 and GSK1120212 in people with Cancer, run by GlaxoSmithKline at 4 sites in 3 countries.
Trial summary
This is a Phase I, open-label, dose-escalation study to characterize the safety, tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in subjects with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- GSK2126458 and GSK1120212
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 3 Dec 2010to 23 Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female 18 years or older at the time of signing the informed consent.
- Confirmed diagnosis of certain molecular types of colorectal , pancreatic, endometrial, ovarian, breast or bladder cancers or melanoma for which there is no approved or curative treatment. Subjects who refuse standard treatment may be included. Physicians should contact the GSK medical monitor for details about the types of tumors that may be treated in this study.
- All prior treatment related toxicities must be CTCAE (Version 4.0) ≤ Grade 1 (except alopecia) at the time of treatment allocation
- Adequate organ system function.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Able to swallow and retain orally administered medication
- Subjects with prior Whipple procedure
- Female or male that is willing to take measures to avoid pregnancy in self or a partner, including abstinence, or double barrier method.
Who cannot join
- Primary malignancy of the CNS or malignancies related to HIV or solid organ transplant. History of known HIV, known Hepatitis B surface antigen or positive Hepatitis C antibody.
- Chemotherapy, extensive radiotherapy, major surgery, anti-neoplastic antibody or targeted therapy or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of investigational products.
- Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of the investigational products.
- Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy, such as: evidence of new optic disc cupping, evidence of new visual field defects or intraocular pressure >21 mm Hg measured by tonography.
- Current use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 14 days prior to the first dose of GSK1120212 or GSK2126458. Low dose (prophylactic) low molecular weight heparin and warfarin are permitted drugs.
- Current use of a prohibited medication
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- Previously diagnosed with diabetes mellitus (Type 1 or 2) or steroid-induced hyperglycemia.
- Evidence of severe or uncontrolled systemic diseases.
- 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.
- Brain metastases, unless previously treated brain metastases with surgery, whole brain radiation, or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size) for at least 8 weeks with two consecutive MRI scans using contrast prior to dosing with investigational product.
- History of acute coronary syndromes coronary angioplasty, or stenting within the past 6 months.
- History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association.
- QTcF interval > or = 470 msecs. History or evidence of current clinically significant uncontrolled arrhythmias. ubjects wtih controlled atrial fibrillation for > 1 month are eligible.
- Treatment refractory hypertension defined as systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg
- Subjects with intra-cardiac defibrillators or permanent pacemakers
- Known cardiac metastases
- Hypersensitivity to study drugs
- Pregnant females or lactating females.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
GSK Investigational Site
Chapel Hill, North Carolina, 27599-7305
GSK Investigational Site
Nashville, Tennessee, 37203
About this study
Official title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK2126458 and GSK1120212 Combination Therapy in Subjects With Advanced Solid Tumors.
This is a Phase I, open-label, dose-escalation study to characterize the safety, tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in subjects with advanced solid tumors. The study will be conducted in 2 parts, a dose escalation phase and a tumor specific cohort expansion.
Read the detailed description
This is a Phase I, open-label, dose-escalation study to characterize the safety, tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in subjects with advanced solid tumors. The study will be conducted in 2 parts, a Part 1 dose escalation phase and a Part 2 tumor specific cohort expansion.
A continuous daily dosing schedule will be utilized initially for both investigational products. The frequency and schedule of dosing may be adjusted based on emerging safety, pharmacokinetics, and pharmacodynamics data.
Once a recommended regimen has been characterized in Part 1, it may be further evaluated in Part 2 . More than one regimen (doses and schedules) may be evaluated in Part 2, based on findings in Part 1.
Subjects eligible for enrollment in Part 2 will have solid tumors with genetic profiles that are likely to benefit from a MEK and PI3K pathway inhibition.
- Conditions
- Cancer
- Being tested
- GSK2126458 and GSK1120212
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2126458 and GSK1120212Drug
GSK2126458 and GSK1120212 are experimental treatments for patients with cancer.
| Study group | Role | What they receive |
|---|---|---|
| GSK2126458 and GSK1120212 | Experimental | The first combination schedule that will be tested involves giving both GSK2126458 and GSK1120212 continuously once a day in the morning until the subjects withdraw from the study. Other dosing schedules with both drugs will also be tested and these schedules are described below GSK2126458 will be dosed twice per day (morning and evening) continuously and GSK1120212 will be dosed once a day in the morning on a continuous schedule. Subjects will be treated with both drugs and remain in the study as long as they are benefiting from therapy. Another schedule that will be tested involves giving GSK2126458 twice each day (morning and evening) on an intermittent schedule (4 days of treatment, 10 days rest, then 4 days treatment, 10 days rest). GSK1120212 will be dosed once each day in the morning on a continuous schedule. Subjects will be treated with both drugs as long as they are benefiting from therapy. Receives: Drug: GSK2126458 and GSK1120212 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the safety of GSK2126458 and GSK1120212 dosed orally in combination through adverse event assessment and changes in safety assessments including laboratory parameters, vital signs, and ECG parameters.
Measured: Subjects continue on study until disease progression or consent withdrawn.
Secondary outcomes (2)
To characterize the tolerability of GSK2126458 and GSK1120212 dosed orally in combination through adverse event assessment and changes in safety assessments including laboratory parameters, vital signs, and ECG parameters.
Measured: Subjects continue on study until disease progression or consent withdrawn.
To determine the recommended Phase II regimen(s) of GSK2126458 and GSK1120212 dosed orally in combination based on safety, tolerability, PK and PD markers (e.g. changes from baseline in biomarkers of pathway inhibition).
Measured: Subjects continue on study until disease progression or consent withdrawn.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2010 (estimated)
- Study start3 Dec 2010
- Primary completion30 Jan 2014
- Study completion23 Apr 2015
Why it stopped: The reason for termination was lack of tolerability and efficacy of the combination treatment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01248858
- Sponsor's protocol ID
- 113794
- Status last verified
- May 2017
- First submitted
- 18 Nov 2010
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK2126458 and GSK1120212 Combination Therapy in Subjects With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT01248858
- Acronym / sponsor ID
- 113794
- Conditions
- Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The reason for termination was lack of tolerability and efficacy of the combination treatment
- Enrolment
- 69 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2010 (actual)
- Primary completion
- 30 Jan 2014 (actual)
- Study completion
- 23 Apr 2015 (actual)
- First posted
- 25 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, open-label, dose-escalation study to characterize the safety, tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in subjects with advanced solid tumors. The study will be conducted in 2 parts, a dose escalation phase and a tumor specific cohort expansion.
Detailed description
This is a Phase I, open-label, dose-escalation study to characterize the safety, tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in subjects with advanced solid tumors. The study will be conducted in 2 parts, a Part 1 dose escalation phase and a Part 2 tumor specific cohort expansion.
A continuous daily dosing schedule will be utilized initially for both investigational products. The frequency and schedule of dosing may be adjusted based on emerging safety, pharmacokinetics, and pharmacodynamics data.
Once a recommended regimen has been characterized in Part 1, it may be further evaluated in Part 2 . More than one regimen (doses and schedules) may be evaluated in Part 2, based on findings in Part 1.
Subjects eligible for enrollment in Part 2 will have solid tumors with genetic profiles that are likely to benefit from a MEK and PI3K pathway inhibition.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2126458 and GSK1120212 | Experimental | Drug: GSK2126458 and GSK1120212The first combination schedule that will be tested involves giving both GSK2126458 and GSK1120212 continuously once a day in the morning until the subjects withdraw from the study. Other dosing schedules with both drugs will also be tested and these schedules are described below GSK2126458 will be dosed twice per day (morning and evening) continuously and GSK1120212 will be dosed once a day in the morning on a continuous schedule. Subjects will be treated with both drugs and remain in the study as long as they are benefiting from therapy. Another schedule that will be tested involves giving GSK2126458 twice each day (morning and evening) on an intermittent schedule (4 days of treatment, 10 days rest, then 4 days treatment, 10 days rest). GSK1120212 will be dosed once each day in the morning on a continuous schedule. Subjects will be treated with both drugs as long as they are benefiting from therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female 18 years or older at the time of signing the informed consent.
- Confirmed diagnosis of certain molecular types of colorectal , pancreatic, endometrial, ovarian, breast or bladder cancers or melanoma for which there is no approved or curative treatment. Subjects who refuse standard treatment may be included. Physicians should contact the GSK medical monitor for details about the types of tumors that may be treated in this study.
- All prior treatment related toxicities must be CTCAE (Version 4.0) ≤ Grade 1 (except alopecia) at the time of treatment allocation
- Adequate organ system function.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
Key exclusion criteria (18 listed)
- Primary malignancy of the CNS or malignancies related to HIV or solid organ transplant. History of known HIV, known Hepatitis B surface antigen or positive Hepatitis C antibody.
- Chemotherapy, extensive radiotherapy, major surgery, anti-neoplastic antibody or targeted therapy or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of investigational products.
- Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of the investigational products.
- Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy, such as: evidence of new optic disc cupping, evidence of new visual field defects or intraocular pressure >21 mm Hg measured by tonography.
- Current use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 14 days prior to the first dose of GSK1120212 or GSK2126458. Low dose (prophylactic) low molecular weight heparin and warfarin are permitted drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2126458 and GSK1120212GSK2126458 and GSK1120212 are experimental treatments for patients with cancer. | Drug | GSK2126458 and GSK1120212 |
Primary outcome
To characterize the safety of GSK2126458 and GSK1120212 dosed orally in combination through adverse event assessment and changes in safety assessments including laboratory parameters, vital signs, and ECG parameters.
Time frame: Subjects continue on study until disease progression or consent withdrawn.
2 secondary outcomes
To characterize the tolerability of GSK2126458 and GSK1120212 dosed orally in combination through adverse event assessment and changes in safety assessments including laboratory parameters, vital signs, and ECG parameters.
Time frame: Subjects continue on study until disease progression or consent withdrawn.
To determine the recommended Phase II regimen(s) of GSK2126458 and GSK1120212 dosed orally in combination based on safety, tolerability, PK and PD markers (e.g. changes from baseline in biomarkers of pathway inhibition).
Time frame: Subjects continue on study until disease progression or consent withdrawn.
Results and safety
The study was stopped early (reason given: The reason for termination was lack of tolerability and efficacy of the combination treatment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Results for study 113794 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2126458 and GSK1120212 in people with Cancer, run by GlaxoSmithKline at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Canada, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The reason for termination was lack of tolerability and efficacy of the combination treatment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize the safety of GSK2126458 and GSK1120212 dosed orally in combination through adverse event assessment and changes in safety assessments including laboratory parameters, vital signs, and ECG parameters. (time frame: Subjects continue on study until disease progression or consent withdrawn.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2017.