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Malignant MelanomaPhase 1NCT01107418

A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

A Phase 1 study testing RO5185426 in people with Malignant Melanoma, run by Hoffmann-La Roche at 13 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

This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
RO5185426
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
13 sitesin 2 countries
Study dates
May 2010to Feb 2013
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

  • adult patients, >/=18 years of age
  • histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
  • failure of at least one prior standard of care regimen
  • positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
  • ECOG performance status 0 or 1
  • adequate hematologic, renal and liver function

Who cannot join

  • active CNS lesions on CT/MRI within 28 days prior to enrollment
  • history of spinal cord compression o carcinomatous meningitis
  • anticipated or ongoing anti-cancer therapies other than those administered in this study
  • previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  • severe cardiovascular disease within 6 months prior to study
  • previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

United States11 sites

  • Study site

    Charlottesville, Virginia, 22908

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Columbus, Ohio, 43219

  • Study site

    East Providence, Rhode Island, 02915

  • Study site

    La Jolla, California, 92093

  • Study site

    New Haven, Connecticut, 06510-3289

  • Study site

    Omaha, Nebraska, 68114

  • Study site

    Park Ridge, Illinois, 60068

  • Study site

    San Francisco, California, 94115

  • Study site

    Sioux City, Iowa, 51101

  • Study site

    Stanford, California, 94305

Other trials in United States

Australia2 sites

  • Study site

    Adelaide, South Australia, 5000

  • Study site

    Melbourne, Victoria, 3181

Other trials in Australia

About this study

Official title: A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients

This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.

Being tested
RO5185426
Medical subject headings
Melanoma

What participants receive

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

  • RO5185426Drug

    dosage b) orally twice daily, days 1-15 (morning dose)

  • RO5185426Drug

    dosage c) orally twice daily, days 1-15 (morning dose)

  • RO5185426Drug

    dosage d) orally twice daily, days 1-15 (morning dose)

  • RO5185426Drug

    960 mg orally twice daily, from day 22 onward

  • RO5185426Drug

    dosage a) orally twice daily, days 1-15 (morning dose)

Study groups in NCT01107418
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: RO5185426
2ExperimentalNot described
Receives: Drug: RO5185426
3ExperimentalNot described
Receives: Drug: RO5185426
4ExperimentalNot described
Receives: Drug: RO5185426

What is being measured

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

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  2. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1

  3. Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  4. Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  6. Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  7. Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

  8. Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15

  9. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15

  10. Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  11. Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  12. Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  13. Apparent Clearance (CL/F) of Vemurafenib on Day 15

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  14. Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15

    Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).

    Measured: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

  15. Accumulation Ratio of Vemurafenib on Day 15

    Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.

    Measured: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15

Secondary outcomes (2)

  1. Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)

    Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.

    Measured: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

  2. Overall Survival (OS)

    OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.

    Measured: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

Timeline

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

  1. First posted21 Apr 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionFeb 2013
  4. Study completionFeb 2013

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
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01107418
Sponsor's protocol ID
NP25163
Status last verified
Jul 2015
First submitted
12 Apr 2010
Last updated
26 Aug 2015

Publications

  • Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.

    PubMed 24983357

  • Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.

    PubMed 23457002

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO5185426 in people with Malignant Melanoma, run by Hoffmann-La Roche at 13 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 6 inclusion and 6 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 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 26 Aug 2015). 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 From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 (time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1). The study lists 15 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 NCT01107418, which also lists 2 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 26 Aug 2015.

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