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NCT Number: NCT01107418

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

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.

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Key information

Conditions

Malignant Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Adelaide, South Australia, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

RO5185426

Drug

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

Primary outcomes

  1. 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

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

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

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

    Time frame: 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

    Time frame: 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

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

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose 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.

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

    Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose 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).

  15. Accumulation Ratio of Vemurafenib on Day 15

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

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

Secondary outcomes

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

    Time frame: 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)

    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.

  2. Overall Survival (OS)

    Time frame: 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)

    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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Apr 21, 2010
Registry last updated
Aug 26, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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