Solid TumoursPhase 1FTIHNCT00972686
Dose-Escalation Study of GSK2126458
A Phase 1 study testing GSK2126458 in people with Solid Tumours, run by GlaxoSmithKline at 9 sites in 2 countries.
Trial summary
P3K112826 is a Phase I, first-time-in-human dose escalation study in subjects with refractory malignancy. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumours
- What is being tested?
- GSK2126458
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 31 Aug 2009to 31 Mar 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
- Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy, or lymphoma
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Female or male that is willing to take measures to avoid pregnancy in self or a partner, including abstinence, or double barrier method.
- Adequate organ system function
Who cannot join
- Use of an investigational anti-cancer medication within 28 days or 5 half-lives preceding the first dose of GSK2126458.
- Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C
- Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
- Prior use of any PI3K inhibitor.
- Current use of a prohibited medication or requires any of these medications during treatment with GSK2126458.
- Presence of an active gastrointestinal disease or other condition known to interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
Show all 13Show fewer
- Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia.
- QTc interval ≥ 480 msecs.
- History of acute coronary syndromes; Class II, III, or IV heart failure; stroke or subarachnoid hemorrhage.
- Systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg.
- Previously diagnosed Type 1 diabetes mellitus. Subjects with Type 2 diabetes are prohibited in the dose escalation part of the study.
- Symptomatic or untreated leptomeningeal or brain metastases.
- Primary malignancy of the central nervous system.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States7 sites
GSK Investigational Site
Chapel Hill, North Carolina, 27599-7600
GSK Investigational Site
Dallas, Texas, 75246
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
New Brunswick, New Jersey, 08901
GSK Investigational Site
Salt Lake City, Utah, 84112-5550
GSK Investigational Site
San Francisco, California, 94115
GSK Investigational Site
Seattle, Washington, 98109
Netherlands2 sites
GSK Investigational Site
Amsterdam, 1066 CX
GSK Investigational Site
Utrecht, 3584 CX
About this study
Official title: A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK2126458 in Subjects With Solid Tumors or Lymphoma
P3K112826 is a Phase I, first-time-in-human dose escalation study in subjects with refractory malignancy. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.
Read the detailed description
This study is a Phase I, first-time-in-human dose escalation study in subjects with refractory solid tumors or lymphoma. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.
Subjects with solid tumors or lymphoma will initially receive oral GSK2126458 daily for 28 consecutive days in each 28 day cycle. Subjects may be dosed once or twice a day or may be dosed on an intermittent schedule depending on the safety, pharmacokinetic and pharmacodynamic results that become available as the study progresses. The starting dose will be 0.1 mg once a day. Expansion of some cohorts will be conducted to test tumor pharmacodynamics, further explore the toxicity profile and to look for preliminary evidence of activity in subjects with tumors with PIK3CA mutations. The recommended Phase II dose will be the lowest dose explored (at or below MTD) that maintains biologic activity with an acceptable tolerability profile.
- Conditions
- Solid Tumours
- Being tested
- GSK2126458
- Keywords
- solid tumors, lymphoma, Phosphoinositide 3-kinase inhibitor
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2126458Drug
GSK2126458 is an experimental treatment for patients with cancer.
| Study group | Role | What they receive |
|---|---|---|
| GSK2126458 | Experimental | GSK2126458 will be dosed continuously (every day) for the duration a 28 day cycle. The 28 day cycles will continue until the subjects withdraw from the study. Receives: Drug: GSK2126458 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs) and changes in laboratory values and vital signs. Pharmacokinetic parameter values for GSK2126458, Change from baseline in protein markers in tumor and/or blood. Blood glucose and insulin levels. Tumor response, RECIST defined
Measured: Subjects continue on study until disease progression or consent withdrawal
Secondary outcomes (1)
Metabolic profile in plasma at the maximum tolerated dose
Measured: Subjects continue on study until disease progression or consent withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2009 (estimated)
- Study start31 Aug 2009
- Primary completion12 Dec 2012
- Study completion31 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumoursStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 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
- NCT00972686
- Sponsor's protocol ID
- 112826
- Acronym
- FTIH
- Status last verified
- May 2017
- First submitted
- 3 Sep 2009
- Last updated
- 9 May 2017
- Results posted
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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 of the Phosphoinositide 3-Kinase Inhibitor GSK2126458 in Subjects With Solid Tumors or Lymphoma
- ClinicalTrials.gov ID
- NCT00972686
- Acronym / sponsor ID
- FTIH / 112826
- Conditions
- Solid Tumours
- Keywords
- solid tumors, lymphoma, Phosphoinositide 3-kinase inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2009 (actual)
- Primary completion
- 12 Dec 2012 (actual)
- Study completion
- 31 Mar 2015 (actual)
- First posted
- 7 Sep 2009 (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.
P3K112826 is a Phase I, first-time-in-human dose escalation study in subjects with refractory malignancy. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.
Detailed description
This study is a Phase I, first-time-in-human dose escalation study in subjects with refractory solid tumors or lymphoma. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.
Subjects with solid tumors or lymphoma will initially receive oral GSK2126458 daily for 28 consecutive days in each 28 day cycle. Subjects may be dosed once or twice a day or may be dosed on an intermittent schedule depending on the safety, pharmacokinetic and pharmacodynamic results that become available as the study progresses. The starting dose will be 0.1 mg once a day. Expansion of some cohorts will be conducted to test tumor pharmacodynamics, further explore the toxicity profile and to look for preliminary evidence of activity in subjects with tumors with PIK3CA mutations. The recommended Phase II dose will be the lowest dose explored (at or below MTD) that maintains biologic activity with an acceptable tolerability profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2126458 | Experimental | Drug: GSK2126458GSK2126458 will be dosed continuously (every day) for the duration a 28 day cycle. The 28 day cycles will continue until the subjects withdraw from the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy, or lymphoma
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- Female or male that is willing to take measures to avoid pregnancy in self or a partner, including abstinence, or double barrier method.
- Adequate organ system function
Key exclusion criteria (13 listed)
- Use of an investigational anti-cancer medication within 28 days or 5 half-lives preceding the first dose of GSK2126458.
- Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C
- Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
- Prior use of any PI3K inhibitor.
- Current use of a prohibited medication or requires any of these medications during treatment with GSK2126458.
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 |
|---|---|---|
| GSK2126458GSK2126458 is an experimental treatment for patients with cancer. | Drug | GSK2126458 |
Primary outcome
Adverse events (AEs) and changes in laboratory values and vital signs. Pharmacokinetic parameter values for GSK2126458, Change from baseline in protein markers in tumor and/or blood. Blood glucose and insulin levels. Tumor response, RECIST defined
Time frame: Subjects continue on study until disease progression or consent withdrawal
1 secondary outcome
Metabolic profile in plasma at the maximum tolerated dose
Time frame: Subjects continue on study until disease progression or consent withdrawal
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Results for study 112826 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Related trials for Solid Tumours
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors
Advanced Breast Cancer, Metastatic Breast Cancer (HR+/ HER2-)
Enrolling by invitationObservational study
Collection of Tissue Specimens From Patients With Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members
Neoplasms, Hematologic Neoplasms
Not yet recruitingPhase 2
Psilocybin With Psychotherapy for Improving Chronic Pain in Cancer Patients Requiring Opioids
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm
RecruitingPhase 3
REGN7508 in Adult Participants for Prevention of Cancer-Associated Thrombosis
Cancer-Associated Thrombosis (CAT)
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
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2126458 in people with Solid Tumours, run by GlaxoSmithKline at 9 sites in 2 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 4 inclusion and 13 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: finished, 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 9 sites in United States, Netherlands. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (AEs) and changes in laboratory values and vital signs. Pharmacokinetic parameter values for GSK2126458, Change from baseline in protein markers in tumor and/or blood. Blood glucose and insulin levels. Tumor response, RECIST defined (time frame: Subjects continue on study until disease progression or consent withdrawal). 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.