Malignant MelanomaPhase 1NCT00405587

Safety Study of PLX4032 in Patients With Solid Tumors

A Phase 1 study testing PLX4032 in people with Malignant Melanoma and Colorectal Carcinoma, run by Plexxikon at 7 sites in 2 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 primary objective of this FIH study is to assess the safety and pharmacokinetics of PLX4032 in patients with solid tumors. The secondary objective is to assess the pharmacodynamic activity in paired biopsy specimens obtained from patients with malignant melanoma who have the V600E BRAF oncogenic mutation. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Malignant Melanoma, Colorectal Carcinoma
What is being tested?: PLX4032
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 109 participants
Where: 7 sitesin 2 countries
Study dates: Nov 2006to Feb 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Solid tumors confirmed histologically whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist
Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032
Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved prior to administration of PLX4032
Patients in the Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay
ECOG performance status 0 or 1
Life expectancy ≥ 3 months
Adequate hematologic, hepatic, and renal function

Who cannot join

Brain metastases that are progressing or have been documented to be stable for less than 3 months, or for which systemic corticosteroids are required
Investigational drug use within 28 days of the first dose of PLX4032
Uncontrolled intercurrent illness
Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States5 sites

MD Anderson Cancer Center
Houston, Texas, 77030
University of California Los Angeles
Los Angeles, California, 90095
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

Australia2 sites

Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002
Royal Melbourne Hospital
Parkville, Victoria

Other trials in Australia

About this study

Official title: A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors

Read the detailed description

Activating mutations of the BRAF gene have been observed in a variety of cancers, including 55-68% of malignant melanomas. In general, oncogenic mutations of BRAF correlate with a poor outcome. PLX4032 is a compound that selectively inhibits oncogenic B-Raf kinase.

Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma.

Conditions: Malignant Melanoma, Colorectal Carcinoma
Being tested: PLX4032
Medical subject headings: Melanoma, Colorectal Neoplasms

What participants receive

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

PLX4032Drug
Oral capsules administered BID

Study groups in NCT00405587
Study group	Role	What they receive
PLX4032	Experimental	Open-label, sequential dose escalation Receives: Drug: PLX4032

What is being measured

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

Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Peak Concentration (Cmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Peak Concentration (Cmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 15, pre-morning dose on Day 16
Time to Peak Concentration (Tmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Time to Peak Concentration (Tmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, pre-morning dose on Day 16
AUC of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Mean RO5185426 Accumulation Ratios - Dose Escalation: MBP Formulation
Accumulation ratio is the ratio of AUC (0-8 hour) on Day 15 / AUC (0-8 hour) on Day 1.
Measured: Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Mean RO5185426 Accumulation Ratios - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Accumulation ratio is the ratio of AUC (0-8 hour) on Day 15 / AUC (0-8 hour) on Day 1.
Measured: Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Cmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Cmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Tmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Tmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
AUC of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Cmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Cmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15 and pre-morning dose on Day 16
Tmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Tmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Percentage of Participants With a Confirmed and an Unconfirmed Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST Version (v) 1.0 - Extension: BRAFV600E- Positive Melanoma
BOR of confirmed /unconfirmed (total) response was defined as CR or PR recorded from baseline until disease progression/recurrence according to Response Evaluation Criteria In Solid Tumors (RECIST) v 1.0 criteria. For target lesions (TLs), CR was defined as the disappearance of all TLs, and PR was defined as at least a 30 percent (%) decrease in the sum of longest diameters of the TLs, taking as a reference the baseline (BL) sum of longest diameters. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Confirmed responses were those which were confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Extension: BRAFV600E- Positive CRC
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Confirmed responses were those which were confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: Original Formulation
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: MBP Formulation
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)

Secondary outcomes (11)

Duration of CR or PR Using RECIST v 1.0 - Extension BRAFV600E- Positive Melanoma
Duration of response for participants with confirmed CR or PR was the period of time measured between the date that the criteria for objective CR or PR (whichever status was recorded first) was met, and the first date that recurrent or PD was objectively documented (or death if before progression). PD was at least a 20% increase in the sum of longest diameters of TLs taking as reference the smallest sum of longest diameters recorded since the baseline measurements, or the appearance of one or more new lesion(s). In the event of no disease progression or documented death prior to study termination, analysis cutoff, or initiation of confounding anticancer therapy, duration of response was censored at the date of the last evaluable tumor assessment.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Percentage of Participants With Progression-Free Survival (PFS) Using RECIST v 1.0 - Melanoma Extension Cohort
PFS was the period of time measured from the date of initiation of therapy to the date of the appearance of new metastatic lesions, objective tumor progression, or death if before progression. PD was defined according to the RECIST criteria (v 1.0) as increase by at least 20% in the sum of the longest diameters of each TL, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. For Non-TLs, PD was defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-TLs.
Measured: Month 1, 3, 4, 6, 9, and Last event (350) days
PFS Using RECIST v1.0 - Extension BRAFV600E Positive Melanoma
PFS was the period of time measured from the date of initiation of therapy to the date of the appearance of new metastatic lesions, objective tumor progression, or death if before progression. PD was at least a 20% increase in the sum of longest diameters of TLs taking as reference the smallest sum of longest diameters recorded since the baseline measurements, or the appearance of one or more new lesion(s). For Non-TLs, disease progression was defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-TLs. In the event of no disease progression or documented death prior to study termination, analysis cutoff, or start of confounding anticancer therapy, PFS was censored at the date of the last evaluable tumor assessment.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 421 days)
Percentage of Participants Who Died - Extension: BRAFV600E- Positive Melanoma
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Overall Survival (OS) - Extension: BRAFV600E- Positive Melanoma
OS was the period of time measured from the date of initiation of therapy to the date of the death. In the event of no death prior to study termination or analysis data cutoff, OS was censored at the last known date that the patient was alive as documented on the follow-up case report form. If this date was not available, then the last known alive date from the database was used.
Measured: Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Time to CR or PR Using RECIST v1.0 - Extension: BRAFV600E- Positive Melanoma
Time to CR or PR was defined as the interval between the date of the first treatment to the date of the first documentation of confirmed CR or PR whichever occurred first, and not the date of confirmation at the subsequent tumor assessment. Time to response = Date of first response - initial dose date + 1.
Measured: Screening, BL, and up to 168 days
Mean Dose-Normalized Steady-State AUC of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Measured: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Mean Dose-Normalized Steady-State Cmax of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2 and Day 8, and Day 16
Decrease in Tumor Uptake of 18F-fluorodeoxyglucose (FDG)
Tumor uptake of FDG was assessed by means of positron-emission tomography (PET)
Measured: BL and Day 15
Cmax of RO5185426 - Food Effect
Measured: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2, Day 8, and Day 16
Tumor Levels of Phosphorylated Extracellular Signal-Regulated Kinapse (ERK), Cyclin D1, and Ki-67
The immunohisto-chemical analyses of the expression of phosphorylated ERK, cyclin D1, and Ki-67 in tumor-biopsy specimens was performed using hematoxylin and eosin staining.
Measured: BL and Day 15

Timeline

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

Nov 2006Feb 2016

First posted30 Nov 2006 (estimated)
Study startNov 2006
Primary completionJul 2015
Study completionFeb 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Malignant MelanomaStudies of the same condition, open and under way.
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: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00405587
Sponsor's protocol ID: PLX06-02
Status last verified: Oct 2016
First submitted: 28 Nov 2006
Last updated: 22 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010 Aug 26;363(9):809-19. doi: 10.1056/NEJMoa1002011.
PubMed 20818844
Kopetz S, Desai J, Chan E, Hecht JR, O'Dwyer PJ, Maru D, Morris V, Janku F, Dasari A, Chung W, Issa JP, Gibbs P, James B, Powis G, Nolop KB, Bhattacharya S, Saltz L. Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol. 2015 Dec 1;33(34):4032-8. doi: 10.1200/JCO.2015.63.2497. Epub 2015 Oct 12.
PubMed 26460303
Puzanov I, Amaravadi RK, McArthur GA, Flaherty KT, Chapman PB, Sosman JA, Ribas A, Shackleton M, Hwu P, Chmielowski B, Nolop KB, Lin PS, Kim KB. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression. Eur J Cancer. 2015 Jul;51(11):1435-43. doi: 10.1016/j.ejca.2015.04.010. Epub 2015 May 13.
PubMed 25980594
Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
PubMed 22256804

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors
ClinicalTrials.gov ID: NCT00405587
Acronym / sponsor ID: PLX06-02
Conditions: Malignant Melanoma, Colorectal Carcinoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 109 participants (actual)
Lead sponsor: PlexxikonIndustry (pharma, biotech, devices)
Collaborators: Roche Pharma AG
Study start: Nov 2006
Primary completion: Jul 2015 (actual)
Study completion: Feb 2016 (actual)
First posted: 30 Nov 2006 (estimated)
Results: Posted 22 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
PLX4032	Experimental	Drug: PLX4032Open-label, sequential dose escalation

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Solid tumors confirmed histologically whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist
Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032
Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved prior to administration of PLX4032
Patients in the Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay
ECOG performance status 0 or 1

Key exclusion criteria (4 listed)

Brain metastases that are progressing or have been documented to be stable for less than 3 months, or for which systemic corticosteroids are required
Investigational drug use within 28 days of the first dose of PLX4032
Uncontrolled intercurrent illness
Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption

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
PLX4032Oral capsules administered BID	Drug	PLX4032

Primary outcome

Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Peak Concentration (Cmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Peak Concentration (Cmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 15, pre-morning dose on Day 16
Time to Peak Concentration (Tmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Time to Peak Concentration (Tmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, pre-morning dose on Day 16
AUC of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
AUC of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Mean RO5185426 Accumulation Ratios - Dose Escalation: MBP Formulation
Time frame: Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Accumulation ratio is the ratio of AUC (0-8 hour) on Day 15 / AUC (0-8 hour) on Day 1.
Mean RO5185426 Accumulation Ratios - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Time frame: Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Accumulation ratio is the ratio of AUC (0-8 hour) on Day 15 / AUC (0-8 hour) on Day 1.
Cmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Cmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Tmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Tmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
AUC of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals zero (0) to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
AUC of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
AUC (0-8 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 8 hours post-dose. AUC (0-24 hour) was defined as the area under the plasma concentration-time curve from time equals 0 to 24 hours post-dose. AUC (0-8 hour) and AUC (0-24 hour) were computed using the linear trapezoidal rule.
Cmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Cmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15 and pre-morning dose on Day 16
Tmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Tmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Percentage of Participants With a Confirmed and an Unconfirmed Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST Version (v) 1.0 - Extension: BRAFV600E- Positive Melanoma
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
BOR of confirmed /unconfirmed (total) response was defined as CR or PR recorded from baseline until disease progression/recurrence according to Response Evaluation Criteria In Solid Tumors (RECIST) v 1.0 criteria. For target lesions (TLs), CR was defined as the disappearance of all TLs, and PR was defined as at least a 30 percent (%) decrease in the sum of longest diameters of the TLs, taking as a reference the baseline (BL) sum of longest diameters. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Confirmed responses were those which were confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Extension: BRAFV600E- Positive CRC
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Confirmed responses were those which were confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: Original Formulation
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: MBP Formulation
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
BOR of CR or PR was recorded from baseline until disease progression/recurrence according to RECIST v 1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of longest diameters of the TLs, taking as a reference the BL sum of longest diameters. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with best overall response rate was calculated as the (number of participants with CR or PR) divided by (total number of participants in the cohort), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.

11 secondary outcomes

Duration of CR or PR Using RECIST v 1.0 - Extension BRAFV600E- Positive Melanoma
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Percentage of Participants With Progression-Free Survival (PFS) Using RECIST v 1.0 - Melanoma Extension Cohort
Time frame: Month 1, 3, 4, 6, 9, and Last event (350) days
PFS Using RECIST v1.0 - Extension BRAFV600E Positive Melanoma
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 421 days)
Percentage of Participants Who Died - Extension: BRAFV600E- Positive Melanoma
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Overall Survival (OS) - Extension: BRAFV600E- Positive Melanoma
Time frame: Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Time to CR or PR Using RECIST v1.0 - Extension: BRAFV600E- Positive Melanoma
Time frame: Screening, BL, and up to 168 days
Mean Dose-Normalized Steady-State AUC of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Mean Dose-Normalized Steady-State Cmax of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2 and Day 8, and Day 16
Decrease in Tumor Uptake of 18F-fluorodeoxyglucose (FDG)
Time frame: BL and Day 15
Cmax of RO5185426 - Food Effect
Time frame: Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2, Day 8, and Day 16
Tumor Levels of Phosphorylated Extracellular Signal-Regulated Kinapse (ERK), Cyclin D1, and Ki-67
Time frame: BL and Day 15

Results and safety

Results posted to the registry on 22 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Escalation: Original Formulation	26	0
Dose Escalation: MBP Formulation	30	2
Extension: BRAFV600E- Positive Melanoma	32	10
Extension: BRAFV600E- Positive CRC	21	1

Primary outcome: Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 1 - Dose Escalation: Original Formulation

Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose. Mean (Standard Deviation). Unit: ug*hr/mL

Measure	Dose Escalation: Original Formulation - 200 mg n = 6	Dose Escalation: Original Formulation - 400 mg n = 4	Dose Escalation: Original Formulation - 800 mg n = 4	Dose Escalation: Original Formulation - 1600 mg n = 4
AUC (0-8 hour) (n= 6, 4, 4, 4)	2.02 (1.03)	3.28 (1.66)	4.47 (0.61)	4.23 (2.0)
AUC (0-24 hour) (n= 6, 4, 4, 4)	8.43 (4.84)	14.86 (7.89)	21.66 (10.59)	22.34 (10.59)

Population analysed: Pharmacokinetic (PK) Population: Participants who received all RO5185426 doses without dose reduction up to and including Day 15 and provided at least PK assessments up to and including 8 to 10 hours after first dose on Day 15. Number of participants analyzed=participants evaluable for this outcome; n=participants evaluable for specified category.

Primary outcome: Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 15 - Dose Escalation: Original Formulation

Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose. Mean (Standard Deviation). Unit: ug*hr/mL

Measure	Dose Escalation Original Formulation - 200 mg n = 6	Dose Escalation: Original Formulation - 400 mg n = 3	Dose Escalation: Original Formulation - 800 mg n = 3	Dose Escalation: Original Formulation - 1600 mg n = 4
AUC (0-8 hour) (n=6, 3, 3, 4)	9.37 (6.18)	30.90 (11.44)	30.58 (7.08)	33.89 (17.24)
AUC (0-24 hour) (n= 2, 2, 3, 4)	46.28 (10.47)	105.10 (65.41)	91.01 (26.86)	101.13 (48.40)

Population analysed: PK Population: Participants who received all RO5185426 doses without dose reduction up to and including Day 15 and provided at least PK assessments up to and including 8 to 10 hours after first dose on Day 15. Number of participants analyzed=participants evaluable for this outcome; n=participants evaluable for specified category.

Primary outcome: Peak Concentration (Cmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation

Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8. Mean (Standard Deviation). Unit: Micrograms per milliliter

Measure	Dose Escalation: Original Formulation - 200 mg n = 6	Dose Escalation: Original Formulation - 400 mg n = 4	Dose Escalation: Original Formulation - 800 mg n = 4	Dose Escalation: Original Formulation - 1600 mg n = 3
Value	0.37 (0.2)	0.58 (0.27)	0.85 (0.06)	0.73 (0.38)

Primary outcome: Peak Concentration (Cmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation

Time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 15, pre-morning dose on Day 16. Mean (Standard Deviation). Unit: Micrograms per milliliter

Measure	Dose Escalation: Original Formulation - 200 mg n = 6	Dose Escalation: Original Formulation - 400 mg n = 3	Dose Escalation: Original Formulation - 800 mg n = 3	Dose Escalation: Original Formulation - 1600 mg n = 4
Value	1.34 (0.81)	4.57 (2.07)	5.41 (2.26)	5.34 (3.04)

11 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Escalation: MBP Formulation - 160 mg	0 of 4 (0%)	4 of 4 (100%)	Not reported
Dose Escalation: MBP Formulation - 240 mg	2 of 4 (50%)	4 of 4 (100%)	Not reported
Dose Escalation: MBP Formulation - 320 mg	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
Dose Escalation: MBP Formulation - 360 mg	3 of 5 (60%)	5 of 5 (100%)	Not reported
Dose Escalation: MBP Formulation - 720 mg	1 of 7 (14.3%)	7 of 7 (100%)	Not reported
Dose Escalation: MBP Formulation - 1120 mg	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Dose Escalation: Original Formulation - 200 mg	0 of 6 (0%)	6 of 6 (100%)	Not reported
Dose Escalation: Original Formulation - 400 mg	0 of 6 (0%)	6 of 6 (100%)	Not reported
Dose Escalation: Original Formulation - 800 mg	0 of 10 (0%)	10 of 10 (100%)	Not reported
Dose Escalation: Original Formulation - 1600 mg	0 of 4 (0%)	4 of 4 (100%)	Not reported
Extension: BRAFV600E-Positive Melanoma	18 of 32 (56.3%)	32 of 32 (100%)	Not reported
Extension: BRAFV600E-Positive CRC	9 of 21 (42.9%)	21 of 21 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 20818844Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010 Aug 26;363(9):809-19. doi: 10.1056/NEJMoa1002011.
Derived from this study: PubMed 26460303Kopetz S, Desai J, Chan E, Hecht JR, O'Dwyer PJ, Maru D, Morris V, Janku F, Dasari A, Chung W, Issa JP, Gibbs P, James B, Powis G, Nolop KB, Bhattacharya S, Saltz L. Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol. 2015 Dec 1;33(34):4032-8. doi: 10.1200/JCO.2015.63.2497. Epub 2015 Oct 12.
Derived from this study: PubMed 25980594Puzanov I, Amaravadi RK, McArthur GA, Flaherty KT, Chapman PB, Sosman JA, Ribas A, Shackleton M, Hwu P, Chmielowski B, Nolop KB, Lin PS, Kim KB. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression. Eur J Cancer. 2015 Jul;51(11):1435-43. doi: 10.1016/j.ejca.2015.04.010. Epub 2015 May 13.
Derived from this study: PubMed 22256804Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.

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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.

Henry Hsu, MD study director

Plexxikon

7 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 PLX4032 in people with Malignant Melanoma and Colorectal Carcinoma, run by Plexxikon at 7 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 7 inclusion and 4 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 22 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Australia. 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?

Yes. Results are posted in the registry (first posted 22 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 1 - Dose Escalation: Original Formulation (time frame: Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose). The study lists 24 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 NCT00405587, which also lists 4 linked publications.

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 22 Aug 2017.