CancerPhase 1NCT01262963
An Absorption, Distribution, Metabolism and Excretion (ADME) Study of Single Oral Dose [14C] GSK2118436 in Subjects With BRAF Mutant Solid Tumors
A Phase 1 study testing GSK2118436 in people with Cancer, run by GlaxoSmithKline at 1 site in United States.
Trial summary
The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive 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?
- GSK2118436
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jan 2011to 8 Apr 2011
- 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 at least 18 years of age at the time of signing the informed consent form;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
- Body weight >= 45 kg and a body mass index (BMI) >/= 19 kg/m2 and </= 35 kg/m2 (inclusive);
- Able to swallow and retain oral medication;
- BRAF mutation-positive tumor (V600 E/K mutation) as determined via relevant genetic testing;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 [Oken, 1982]; NOTE: Subjects with an ECOG performance status of 2 may be eligible with the approval of the GSK Medical Monitor
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- Women of child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control. Additionally, women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment;
- Must have adequate organ function as defined by the following values:
- Absolute neutrophil count (ANC) >/=1.2 x 10^9/L
- Hemoglobin >/=9 g/dL
- Platelets >/=100 x 10^9/L
- Serum bilirubin </=1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 x ULN; <5 x ULN if liver metastases are present (with approval of GSK medical monitor)
- Serum creatinine </= ULN or calculated creatinine clearance >/= 60 mL/min
- Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) </=1.3 x ULN
- Left ventricular ejection fraction </= institutional lower limit of normal by ECHO
Who cannot join
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last three weeks; chemotherapy regimens without delayed toxicity within the last two weeks; or use of an investigational anti-cancer drug within four weeks preceding the first dose of GSK2118436;
- Current use of a prohibited medication or requires any of these medications during the study;
- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from seven days prior to the first dose of study medication;
- Current use of therapeutic warfarin (note: low molecular weight heparin and prophylactic low-dose warfarin are permitted);
- History of sensitivity to heparin or heparin-induced thrombocytopenia;
- The radiation exposure from the previous three year period is over 10 millisieverts (mSv) for subjects who have been exposed to ionizing radiation above background as a result of their work with radiation as Category A (classified) workers or as a result of research studies they may have been involved in. Subjects will be excluded if exposure levels cannot be verified. Clinical (therapeutic or diagnostic) exposure will not be included;
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- An occupation which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays within the past 12 months;
- Any major surgery within the last four weeks;
- Unresolved toxicity equal to or greater than National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 from previous anti-cancer therapy except alopecia;
- Presence of active gastrointestinal disease or other condition (e.g., gastrectomy, bariatric surgery, small bowel or large bowel resection) that may interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GSK medical monitor for permission to enroll the subject;
- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence HBV clearance may be enrolled with permission of the GSK medical monitor);
- Patients with a history of malignancy that have been definitively treated can be enrolled with approval of the GSK medical monitor;
- Subjects with brain metastases are excluded if their brain metastases are either:
- Symptomatic Treated (surgery, radiation therapy) but not clinically and radiographically stable one month after local therapy, or Asymptomatic and untreated but > 1 cm in the longest dimension Patients with small (</= 1 cm in the longest dimension), asymptomatic brain metastases that do not need immediate local therapy can be enrolled with the approval of the GSK medical monitor. Subjects on a stable dose of corticosteroids for more than one month, or those who have been off corticosteroids for at least two weeks can be enrolled with approval of the GSK medical monitor. Subjects must also be off of enzyme-inducing anticonvulsants for more than four weeks;
- History of alcohol or drug abuse within six months prior to screening;
- Corrected QT (QTc) interval >/= 480 msecs;
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks;
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; abnormal cardiac valve morphology documented by echocardiogram (subjects with minimal abnormalities [ie, mild regurgitation/stenosis] can be entered on study with approval from the GSK medical monitor); or history of known cardiac arrhythmias (except sinus arrhythmias) within the past 24 weeks;
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients (note: to date there are no known drugs chemically related to GSK2118436 which are approved by the Food and Drug Administration);
- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol;
- Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency;
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period;
- Pregnant females as determined by positive pregnancy test at screening or prior to dosing;
- Lactating females who are actively breast feeding;
- Subject is mentally or legally incapacitated;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Study to Characterize the Absorption, Distribution, Metabolism and Elimination of a Single Oral 14C Labeled Dose of GSK2118436 in Subjects With BRAF Mutant Solid Tumors
The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors.
Read the detailed description
GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is being developed for the treatment of BRAF mutation-positive tumors. The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors. A sufficient number of subjects will be enrolled to complete approximately four subjects. Following completion of the study, subjects may continue dosing with GSK2118436 in the rollover study, BRF114144.
- Conditions
- Cancer
- Being tested
- GSK2118436
- Keywords
- GSK2118436, BRAF inhibitor, BRAF positive tumor, ADME, Oncology
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2118436Drug
A single oral dose of 95 mg of GSK2118436 containing approximately 80 µCi of radioactivity
| Study group | Role | What they receive |
|---|---|---|
| Study Medication | Experimental | GSK2118436 suspension Receives: Drug: GSK2118436 |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Excretion of radioactivity in urine following oral administration of [14C]GSK2118436
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Excretion of radioactivity in feces following oral administration of [14C]GSK2118436
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
Secondary outcomes (15)
• Quantity of GSK2118436 metabolites in plasma
Measured: Pre-dose, and up to 48 hours post dose.
• Potential covalent binding of drug-related material to plasma proteins
Measured: Pre-dose, and up to 48 hours post dose.
• Blood total radioactivity
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Blood:plasma ratio of total drug-related material (radioactivity)
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Area under the plasma-concentration time curve (AUC) of plasma GSK2118436 and metabolites
Measured: Pre-dose, and up to 48 hours post dose.
• Number of subjects with adverse events as a measure of safety and tolerability
Measured: From date of dosing until transition to rollover protocol BRF114144 (approximately 4 - 11 days) or study follow up visit if subject does not transition to BRF114144 (approximately 14 - 21 days)
• Quantity of GSK2118436 metabolites in feces
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Quantity of GSK2118436 metabolites in urine
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in plasma
Measured: Pre-dose, and up to 48 hours post dose.
• Character of GSK2118436 metabolites in feces
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in urine
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Plasma total radioactivity
Measured: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Maximum plasma concentration (Cmax) of plasma GSK2118436 and metabolites
Measured: Pre-dose, and up to 48 hours post dose
• Time to Cmax (Tmax) of plasma GSK2118436 and metabolites
Measured: Pre-dose, and up to 48 hours post dose
• Terminal half-life (t1/2) of plasma GSK2118436 and metabolites
Measured: Pre-dose, and up to 48 hours post dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2010 (estimated)
- Study start26 Jan 2011
- Primary completion8 Apr 2011
- Study completion8 Apr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 4 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
- NCT01262963
- Sponsor's protocol ID
- 113463
- Status last verified
- Nov 2017
- First submitted
- 2 Dec 2010
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Bershas DA, Ouellet D, Mamaril-Fishman DB, Nebot N, Carson SW, Blackman SC, Morrison RA, Adams JL, Jurusik KE, Knecht DM, Gorycki PD, Richards-Peterson LE. Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation. Drug Metab Dispos. 2013 Dec;41(12):2215-24. doi: 10.1124/dmd.113.053785. Epub 2013 Oct 4.
PubMed 24097902
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Characterize the Absorption, Distribution, Metabolism and Elimination of a Single Oral 14C Labeled Dose of GSK2118436 in Subjects With BRAF Mutant Solid Tumors
- ClinicalTrials.gov ID
- NCT01262963
- Acronym / sponsor ID
- 113463
- Conditions
- Cancer
- Keywords
- GSK2118436, BRAF inhibitor, BRAF positive tumor, ADME, Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 26 Jan 2011 (actual)
- Primary completion
- 8 Apr 2011 (actual)
- Study completion
- 8 Apr 2011 (actual)
- First posted
- 20 Dec 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.
The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors.
Detailed description
GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is being developed for the treatment of BRAF mutation-positive tumors. The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors. A sufficient number of subjects will be enrolled to complete approximately four subjects. Following completion of the study, subjects may continue dosing with GSK2118436 in the rollover study, BRF114144.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Medication | Experimental | Drug: GSK2118436GSK2118436 suspension |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male or female at least 18 years of age at the time of signing the informed consent form;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
- Body weight >= 45 kg and a body mass index (BMI) >/= 19 kg/m2 and </= 35 kg/m2 (inclusive);
- Able to swallow and retain oral medication;
- BRAF mutation-positive tumor (V600 E/K mutation) as determined via relevant genetic testing;
Key exclusion criteria (26 listed)
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last three weeks; chemotherapy regimens without delayed toxicity within the last two weeks; or use of an investigational anti-cancer drug within four weeks preceding the first dose of GSK2118436;
- Current use of a prohibited medication or requires any of these medications during the study;
- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from seven days prior to the first dose of study medication;
- Current use of therapeutic warfarin (note: low molecular weight heparin and prophylactic low-dose warfarin are permitted);
- History of sensitivity to heparin or heparin-induced thrombocytopenia;
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 |
|---|---|---|
| GSK2118436A single oral dose of 95 mg of GSK2118436 containing approximately 80 µCi of radioactivity | Drug | Study Medication |
Primary outcome
• Excretion of radioactivity in urine following oral administration of [14C]GSK2118436
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Excretion of radioactivity in feces following oral administration of [14C]GSK2118436
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
15 secondary outcomes
• Quantity of GSK2118436 metabolites in plasma
Time frame: Pre-dose, and up to 48 hours post dose.
• Potential covalent binding of drug-related material to plasma proteins
Time frame: Pre-dose, and up to 48 hours post dose.
• Blood total radioactivity
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Blood:plasma ratio of total drug-related material (radioactivity)
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Area under the plasma-concentration time curve (AUC) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose.
• Number of subjects with adverse events as a measure of safety and tolerability
Time frame: From date of dosing until transition to rollover protocol BRF114144 (approximately 4 - 11 days) or study follow up visit if subject does not transition to BRF114144 (approximately 14 - 21 days)
• Quantity of GSK2118436 metabolites in feces
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Quantity of GSK2118436 metabolites in urine
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in plasma
Time frame: Pre-dose, and up to 48 hours post dose.
• Character of GSK2118436 metabolites in feces
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in urine
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Plasma total radioactivity
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Maximum plasma concentration (Cmax) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose
• Time to Cmax (Tmax) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose
• Terminal half-life (t1/2) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose.
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 13 Nov 2017.
- Background: PubMed 24097902Bershas DA, Ouellet D, Mamaril-Fishman DB, Nebot N, Carson SW, Blackman SC, Morrison RA, Adams JL, Jurusik KE, Knecht DM, Gorycki PD, Richards-Peterson LE. Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation. Drug Metab Dispos. 2013 Dec;41(12):2215-24. doi: 10.1124/dmd.113.053785. Epub 2013 Oct 4.
- Results for study 113463 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2118436 in people with Cancer, run by GlaxoSmithKline at 1 site in United States.
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 16 inclusion and 26 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 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
• Excretion of radioactivity in urine following oral administration of [14C]GSK2118436 (time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01262963, which also lists 1 linked publication.
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 13 Nov 2017.