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CancerPhase 1NCT01340833

Determination of the Absolute Bioavailability of GSK2118436 Following a Single Oral Dose Co-Administered With an Intravenous Radiolabelled Microtracer of 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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is currently being developed for the treatment of BRAF mutation-positive tumors. This is an open-label, non-randomized study designed to determine the absolute bioavailability of an oral dose of 150 mg of GSK2118436… 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
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
8 Jun 2011to 12 Sep 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 >/= 19 kg/m2 and </= 35 kg/m2 (inclusive);
  • Able to swallow and retain oral medication;
  • BRAF mutation-positive tumor as determined via relevant genetic testing;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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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:
  • ANC >/=1.2 x 109/L Hemoglobin >/=9 g/dL Platelets >/=100 x 109/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 Serum creatinine </= ULN or calculated creatinine clearance >/= 60 mL/min Prothrombin time / INR and partial thromboplastin time </=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) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436; use of any other investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is warranted by data);
  • Has participated in a 14C human research study in the 12 months prior to administration of study medication;
  • 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 7 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;
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  • Any major surgery within the last 4 weeks;
  • Unresolved toxicity 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., small bowel or large bowel resection) that will 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 enrol the subject;
  • A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with documented laboratory evidence of HBV clearance may be enrolled);
  • Presence of invasive malignancy other than one of the malignancies covered under Inclusion Criterion; subjects with a history of another malignancy that has been definitively treated can be enrolled;
  • Subjects with brain metastases are excluded if their brain metastases are either:
  • Symptomatic Treated (surgery, radiation therapy), but not clinically and radiographically stable for a period of at least one month prior to study entry, or Asymptomatic and untreated but > 1 cm in the longest dimension Exception: Subjects with small (≤ 1 cm in the longest dimension), asymptomatic brain metastases that do not need immediate local therapy can be enrolled. Subjects on a stable dose of corticosteroids for more than one month, or those who have been off corticosteroids for at least 2 weeks can be enrolled. Subjects must also be off of enzyme-inducing anticonvulsants for more than 4 weeks;
  • 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 ECHO [subjects with minimal abnormalities (i.e., mild regurgitation/stenosis) can be entered on study - if clarification is needed as to whether an ECHO abnormality is minimal, please contact the GSK medical monitor); or history of known cardiac arrhythmias (except sinus arrythmias) 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 FDA);
  • Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or history of alcohol or drug abuse within 6 months prior to screening; or unwillingness or inability to follow the procedures required in the protocol;
  • Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency;
  • Donation of blood or blood products in excess of 500 mL within the 56 days prior to administration of study medication;
  • Pregnant females as determined by positive β hCG test at screening or prior to dosing or lactating females who are actively breast feeding;
  • Subject is mentally or legally incapacitated;

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Tacoma, Washington, 98418

Other trials in United States

About this study

GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is currently being developed for the treatment of BRAF mutation-positive tumors. This is an open-label, non-randomized study designed to determine the absolute bioavailability of an oral dose of 150 mg of GSK2118436 co-administered with an intravenous 50 microgram dose of [14C]GSK2118436 in subjects with BRAF mutant solid tumors. Pharmacokinetic samples will be obtained up to 72 hours post-dose. Safety assessments will be performed throughout the study. After completing all assessments, eligible subjects may transition to BRF114144, an open-label, rollover study of GSK2118436 to continue treatment.

Conditions
Cancer
Being tested
GSK2118436
Keywords
GSK2118436, BRAF inhibitor, BRAF-mutation positive tumor, Oncology, absolute bioavailability, microtracer
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2118436Drug

    Two capsules each containing 75 mg GSK2118436, followed by a single IV dose of 50 ug (no more than 7.4 kBq or 200 nCi) [14C]GSK2118436, starting 1.75 hours after the oral dose

Study groups in NCT01340833
Study groupRoleWhat they receive
Study MedicationExperimentalGSK2118436
Receives: Drug: GSK2118436

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The percent of absolute bioavailability (F) of GSK2118436 following single-dose oral HPMC capsule and a concomitant IV microdose

    Measured: Up to 72 hours

Secondary outcomes (8)

  1. Maximum plasma concentration (Cmax) of plasma GSK2118436 and [14C]GSK2118436

    Measured: Up to 72 hours

  2. Time to Cmax (Tmax) of plasma GSK2118436 and [14C]GSK2118436

    Measured: Up to 72 hours

  3. Area under the plasma-concentration time curve (AUC) of plasma GSK2118436 and [14C]GSK2118436

    Measured: Up to 72 hours

  4. Terminal half-life (t1/2) of plasma GSK2118436 and [14C]GSK2118436

    Measured: Up to 72 hours

  5. Oral clearance (CL/F) of GSK2118436

    Measured: Up to 72 hours

  6. Clearance (CL) of [14C]GSK2118436

    Measured: Up to 72 hours

  7. Volume of distribution (Vd) of [14C]GSK2118436

    Measured: Up to 72 hours

  8. 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 days) or study follow up visit if subject does not transition to BRF114144 (approximately 11 - 14 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2011 (estimated)
  2. Study start8 Jun 2011
  3. Primary completion12 Sep 2011
  4. Study completion12 Sep 2011

Resources

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01340833
Sponsor's protocol ID
113479
Status last verified
Nov 2017
First submitted
14 Apr 2011
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Denton CL, Minthorn E, Carson SW, Young GC, Richards-Peterson LE, Botbyl J, Han C, Morrison RA, Blackman SC, Ouellet D. Concomitant oral and intravenous pharmacokinetics of dabrafenib, a BRAF inhibitor, in patients with BRAF V600 mutation-positive solid tumors. J Clin Pharmacol. 2013 Sep;53(9):955-61. doi: 10.1002/jcph.127. Epub 2013 Jul 12.

    PubMed 23846776

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 9 inclusion and 22 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?

The percent of absolute bioavailability (F) of GSK2118436 following single-dose oral HPMC capsule and a concomitant IV microdose (time frame: Up to 72 hours). 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 NCT01340833, 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.

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