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CancerPhase 1NCT01954043

A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors

A Phase 1 study testing Dabrafenib 150 mg twice a day (BID), Rabeprazole 40 mg once daily (OD) and Rifampin 600 mg OD in people with Cancer, run by GlaxoSmithKline at 6 sites in 3 countries.

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

The study is being conducted to evaluate the effect of rifampin (a strong CYP3A4 inducer) and rabeprazole (a pH elevating agent) on the PK of dabrafenib (a CYP3A4/CYP2C8 substrate). The study will be conducted in subjects with BRAF V600 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?
Dabrafenib 150 mg twice a day (BID), Rabeprazole 40 mg once daily (OD) and Rifampin 600 mg OD
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
6 sitesin 3 countries
Study dates
20 Dec 2013to 29 Feb 2016
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.
  • Provided signed written informed consent.
  • Capable of compliance with the requirements and restrictions listed in the consent form.
  • Body weight >=45 kilogram (kg) and a body mass index (BMI) >=19 Kilogram per meter squared (kg/m^2) and <40 kg/m^2 (inclusive).
  • Able to swallow and retain oral medication.
  • BRAF V600 mutation-positive tumor as confirmed in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory or equivalent.
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate baseline organ function defined in study protocol.
  • Women of child-bearing 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 medication.

Who cannot join

  • History of another malignancy with exceptions below, or any malignancy with confirmed activating RAS mutation. Exception: (a) Subjects who have been successfully treated and are disease-free for 5 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score <=6, and PSA <10 nanogram per milliliter [ng/mL]) requiring no or only anti-hormonal therapy, are eligible.
  • Cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) or investigational anti-cancer drugs within the last 3 weeks, or chemotherapy without delayed toxicity within the last 2 weeks, preceding the first dose of dabrafenib.
  • Unresolved toxicity greater than Grade 2 from previous anti-cancer therapy except alopecia.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  • Current use of therapeutic warfarin.
  • Any prohibited medication(s) or herbal preparation as described in study protocol or requires any of these medications during the study.
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  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to dabrafenib, rabeprazole and rifampin, or excipients that contraindicates their participation.
  • Pregnant or nursing females.
  • A history or evidence of cardiovascular risk including any of the following: a QT interval corrected for heart rate using the Bazett's formula (QTcB) >=480 milliseconds (msec); a history or evidence of current clinically significant uncontrolled arrhythmias; a history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; a history or evidence of current >=Class II congestive heart failure (CHF) as defined by the New York Heart Association (NYHA) guidelines; Abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • Presence of active gastrointestinal (GI) 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.
  • A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus infection.
  • Subjects with brain metastases are excluded if their brain metastases are: Symptomatic, Treated (surgery, radiation therapy) but not clinically and radiographically stable one month after local therapy, or asymptomatic and untreated but >1 centimeter (cm) in the longest dimension. 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 >1 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.

Trial locations and contacts

6 sites in 3 countries.

6 sites in 3 countries

United States3 sites

  • GSK Investigational Site

    Dallas, Texas, 75201

  • GSK Investigational Site

    Goodyear, Arizona, 85338

  • GSK Investigational Site

    Tacoma, Washington, 98405

Other trials in United States

Australia2 sites

  • GSK Investigational Site

    Heidelberg, Victoria, 3084

  • GSK Investigational Site

    Melbourne, Victoria, 3004

Other trials in Australia

United Kingdom1 site

  • GSK Investigational Site

    London, W1G 6AD

Other trials in United Kingdom

About this study

Official title: An Open-label Study to Evaluate the Effects of a Potent CYP3A4 Inducer and the Effects of a pH Elevating Agent on the Repeat Dose Pharmacokinetics of Dabrafenib (GSK2118436) in Subjects With BRAF V600 Mutation Positive Tumors

The study is being conducted to evaluate the effect of rifampin (a strong CYP3A4 inducer) and rabeprazole (a pH elevating agent) on the PK of dabrafenib (a CYP3A4/CYP2C8 substrate). The study will be conducted in subjects with BRAF V600 mutation-positive tumors. Data collected from this study will be used to inform recommendations regarding use of concomitant medications with dabrafenib and future clinical pharmacologic evaluation of dabrafenib.

Conditions
Cancer
Being tested
Dabrafenib 150 mg twice a day (BID), Rabeprazole 40 mg once daily (OD), Rifampin 600 mg OD
Keywords
melanoma, dabrafenib, BRAF V600, rabeprazole, rifampin
Medical subject headings
Neoplasms, Melanoma

What participants receive

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

  • Dabrafenib 150 mg twice a day (BID)Drug

    Dabrafenib dosed at 150mg twice a day from Day 1 to the morning of Day 29

  • Rabeprazole 40 mg once daily (OD)Drug

    Rabeprazole dosed at 40mg each morning on Days 16 to 19

  • Rifampin 600 mg ODDrug

    Rifampin dosed at 600mg each morning on Days 20 to 29

Study groups in NCT01954043
Study groupRoleWhat they receive
Arm AExperimentalSubjects will administer Dabrafenib from Day 1 to Day 15, Dabrafenib and Rabeprazole from Day 16 to Day 19, Dabrafenib and Rifampin from Day 20 to Day 29. The serial PK samples will be collected for 12 hours following dosing on Day 15 (Dabrafenib alone), Day 19 (Dabrafenib and Rabeprazole), and Day 29 (Dabrafenib and Rifampin).
Receives: Drug: Dabrafenib 150 mg twice a day (BID); Drug: Rabeprazole 40 mg once daily (OD); Drug: Rifampin 600 mg OD

What is being measured

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

  1. PK assessment (Cmax) of Dabrafenib with and without Rabeprazole or Rifampin

    Blood samples will be collected to assess PK parameters including: maximum observed concentration (Cmax)

    Measured: Day 15, 19 and Day 29

  2. PK assessment (tmax) of Dabrafenib with and without Rabeprazole or Rifampin

    Blood samples will be collected to assess PK parameters including: time to Cmax (tmax)

    Measured: Day 15, 19 and Day 29

  3. PK assessment (AUC[0-tau]) of Dabrafenib with and without Rabeprazole or Rifampin

    Blood samples will be collected to assess PK parameters including: area under the concentration-time curve over the dosing interval (AUC[0-tau])

    Measured: Day 15, 19 and Day 29

Secondary outcomes (11)

  1. PK assessment of Dabrafenib co administered with rabeprazole or rifampin

    Blood samples will be collected to assess PK parameters including: Pre-dose concentration (Ctau) after administration of Dabrafenib co-administered with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  2. PK assessment (AUC[0-tau]) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib

    Blood samples will be collected to assess PK parameter (AUC[0-tau]) after administration of Dabrafenib co-administered with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  3. PK assessment (Cmax and Ctau,) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib

    Blood samples will be collected to assess PK parameters including: Cmax and Ctau, after administration of Dabrafenib co-administered with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  4. PK assessment (tmax) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib

    Blood samples will be collected to assess PK parameter (tmax), after administration of Dabrafenib co-administered with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  5. Ratio of metabolite to Dabrafenib

    Blood samples will be collected for AUC(0 tau) to estimate ratio of Dabrafenib metabolites to parent Dabrafenib co-administered with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  6. Safety and tolerability assessment to measure vital signs

    Safety and tolerability assessment for vital signs including systolic and diastolic blood pressure, temperature, and pulse rate for dabrafenib in combination with rabeprazole or rifampin

    Measured: Day 15, 19 and Day 29

  7. Safety and tolerability assessment for 12-lead ECG

    A single 12-lead ECG will be obtained to assess safety and tolerability of dabrafenib in combination with rabeprazole or rifampin

    Measured: From Screening up to follow up visit within 7-10 days of the last dose of study medication

  8. Safety and tolerability assessment for laboratory tests

    Safety and tolerability assessment for clinical laboratory tests including hematology, clinical chemistry and other tests for dabrafenib in combination with rabeprazole or rifampin

    Measured: From Screening up to follow up visit within 7-10 days of the last dose of study medication

  9. Safety and tolerability assessment of dabrafenib in combination with rabeprazole or rifampin

    Safety and tolerability assessment includes adverse events (AEs) and serious adverse events (SAEs)

    Measured: From Screening up to follow up visit within 7-10 days of the last dose of study medication

  10. Concentrations of Rabeprazole in the presence of Dabrafenib

    Blood sample will be collected to measure concentration of Rabeprazole in the presence of Dabrafenib

    Measured: Predose, 1, 2, 3 and 12 hours postdose on Day 19

  11. Concentrations of Rifampin in the presence of Dabrafenib

    Blood sample will be collected to measure concentration of Rifampin in the presence of Dabrafenib

    Measured: Predose, 1, 2, 3 and 12 hours postdose on Day 29

Timeline

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

  1. First posted1 Oct 2013 (estimated)
  2. Study start20 Dec 2013
  3. Primary completion29 Feb 2016
  4. Study completion29 Feb 2016

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01954043
Sponsor's protocol ID
200072
Status last verified
Nov 2017
First submitted
26 Sep 2013
Last updated
14 Nov 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dabrafenib 150 mg twice a day (BID), Rabeprazole 40 mg once daily (OD) and Rifampin 600 mg OD in people with Cancer, run by GlaxoSmithKline at 6 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 9 inclusion and 12 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 14 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 6 sites in United States, Australia, United Kingdom. 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?

PK assessment (Cmax) of Dabrafenib with and without Rabeprazole or Rifampin (time frame: Day 15, 19 and Day 29). The study lists 3 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 NCT01954043.

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 14 Nov 2017.

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