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NeoplasmsPhase 1NCT01767623

A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Participants

A Phase 1 study testing Vemurafenib in people with Neoplasms, run by Hoffmann-La Roche at 8 sites in 7 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

This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the pharmacokinetics and safety of vemurafenib in participants with BRAF V600 mutation positive cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Vemurafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
8 sitesin 7 countries
Study dates
20 Aug 2013to 20 Apr 2017
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 confirmed BRAF V600 mutation-positive advanced solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • Normal or impaired hepatic function (hepatic function will be classified according to the NCI Organ Dysfunction Working Group criteria)
  • For participants with hepatic impairment: Stable hepatic function for at least 2 weeks (greater than [>] 14 days) before Day 1
  • Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (</=) 2
  • Participants with a history of recent brain metastases must have completed any radiation therapy at least 4 weeks before Day 1, be without intervening signs of brain lesion progression and not require steroids before starting the protocol (Day 1). Participants with gliomas or known brain metastases who require anticonvulsants must be seizure free for 1 month prior to enrollment
  • Life expectancy greater than or eual to (>/=) 8 weeks
  • Adequate hematologic and renal function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (<) 1 percent per year during the treatment period and for at least 6 months after the last dose of study drug

Who cannot join

  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Requirement for immediate or urgent treatment with twice a day vemurafenib and for whom the intermittent schedule of vemurafenib employed during Days 1-26 of this trial is not clinically acceptable
  • Chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from AEs because of agents administered more than 4 weeks earlier
  • Gliomas or known brain metastases that require corticosteroids
  • History of clinically significant cardiac or pulmonary dysfunction
  • Human Immunodeficiency Virus (HIV)-positive participant requiring antiviral treatment including protease inhibitors
Show all 11Show fewer
  • Active infection or chronic infection requiring chronic suppressive antibiotics
  • Pregnancy or breastfeeding at Day 1
  • History of malabsorption or other clinically significant metabolic dysfunction
  • Active autoimmune disease
  • Current, recent (within 28 days prior to Day 1), or planned use of any investigational product outside this study

Trial locations and contacts

8 sites in 7 countries.

8 sites in 7 countries

Israel2 sites

  • Rambam Health Care Campus

    Haifa, 31096

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

Other trials in Israel

United States1 site

  • California Cancer Associates for Research & Excellence, Inc.

    Encinitas, California, 92008

Other trials in United States

Australia1 site

  • Peninsula and South Eastern Haematology and Oncology Grou

    Frankston, Victoria, 3199

Other trials in Australia

Greece1 site

  • District General Hospital of Athens Laiko; 1st Internal Medicine Clinic

    Athens, 11527

Other trials in Greece

Russia1 site

  • SBIH " Clinical Oncological Dispensary # 1"; Chemotherapy department #1 and #2

    Krasnodar, 350040

Other trials in Russia

Turkey (Türkiye)1 site

  • Ege University Medicine Develoment and Pharmacokinetics Research Center; Pulmonary Diseases

    Izmir, 35040

Other trials in Turkey (Türkiye)

United Kingdom1 site

  • Velindre Cancer Centre

    Cardiff, CF14 2TL

Other trials in United Kingdom

About this study

Official title: An Open Label, Phase I Study to Evaluate the Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation Positive Cancer Patients

This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the pharmacokinetics and safety of vemurafenib in participants with BRAF V600 mutation positive cancer. Participants will receive vemurafenib 960 milligrams (mg) (normal hepatic function) or 720 mg (severe hepatic impairment) orally twice daily (BID) on Days 1 to 20 (morning dose) and from Day 27 onward until disease progression or unacceptable toxicity occurs.

Conditions
Neoplasms
Being tested
Vemurafenib
Medical subject headings
Neoplasms

What participants receive

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

  • VemurafenibDrug

    Also called RO5185426, Zelboraf®

    Vemurafenib orally BID 960 or 720 mg.

Study groups in NCT01767623
Study groupRoleWhat they receive
Cohort 1: Participants with Normal Liver FunctionActive comparatorParticipants with normal liver function (according to National Cancer Institute [NCI] liver dysfunction criteria) will receive vemurafenib 960 mg BID from Day 1 until the morning dose on Day 20 and then from Day 27 onward until disease progression, safety-related treatment termination, withdrawal of consent, death, or a decision by the Sponsor to terminate the study, whichever occurs first.
Receives: Drug: Vemurafenib
Cohort 2: Participants with Severe Liver DysfunctionExperimentalParticipants with severe liver dysfunction (according to NCI liver dysfunction criteria) will receive vemurafenib 720 mg BID from Day 1 until the morning dose on Day 20 and then from Day 27 onward until disease progression, safety-related treatment termination, withdrawal of consent, death, or a decision by the Sponsor to terminate the study, whichever occurs first.
Receives: Drug: Vemurafenib

What is being measured

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

  1. Dose-Normalized Area Under the Concentration-Time Curve (AUC) of Vemurafenib During the Dose Interval (12 hours) (AUCtau) on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

  2. Dose-Normalized Maximum Observed Concentration (Cmax) of Vemurafenib on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

Secondary outcomes (9)

  1. Percentage of Participants with Adverse Events (AEs)

    Measured: Baseline up to approximately 3 years

  2. Dose-Normalized AUCtau of of Vemurafenib on Day 1

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1

  3. Dose-Normalized AUC from Time 0 to Last Measurable Concentration Time Point (AUC0-last) of Vemurafenib on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

  4. Dose-Normalized AUC from Time 0 to Infinity (AUC0-∞) of Vemurafenib on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

  5. Dose-Normalized Cmax of Vemurafenib on Day 1

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1

  6. Time to Maximum Concentration (tmax) of Vemurafenib on Day 1 and Day 20

    Measured: Day 1: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose; Day 20: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose

  7. Half-life (t1/2) of Vemurafenib in Plasma on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

  8. Dose Normalized Apparent Clearance (CL/F) of Vemurafenib on Day 20

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20

  9. Trough Plasma Concentration (Cmin or Ctrough) of Vemurafenib

    Measured: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1; Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20; Before the morning dose on Days 9 and 15

Timeline

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

  1. First posted14 Jan 2013 (estimated)
  2. Study start20 Aug 2013
  3. Primary completion20 Apr 2017
  4. Study completion20 Apr 2017

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
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01767623
Sponsor's protocol ID
GO28053
Other IDs
2012-003820-18
Status last verified
Feb 2018
First submitted
11 Jan 2013
Last updated
13 Feb 2018
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vemurafenib in people with Neoplasms, run by Hoffmann-La Roche at 8 sites in 7 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 11 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 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Israel, United States, Australia, Greece, Russia and 2 more countries. 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?

Dose-Normalized Area Under the Concentration-Time Curve (AUC) of Vemurafenib During the Dose Interval (12 hours) (AUCtau) on Day 20 (time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20). 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 NCT01767623.

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 Feb 2018.

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