A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
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ClinicalTrials.gov Identifier: NCT01107418 |
Recruitment Status :
Completed
First Posted : April 21, 2010
Results First Posted : August 26, 2015
Last Update Posted : August 26, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Malignant Melanoma | Drug: RO5185426 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 52 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Study Start Date : | May 2010 |
Actual Primary Completion Date : | February 2013 |
Actual Study Completion Date : | February 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: 1 |
Drug: RO5185426
960 mg orally twice daily, from day 22 onward Drug: RO5185426 dosage a) orally twice daily, days 1-15 (morning dose) |
Experimental: 2 |
Drug: RO5185426
dosage b) orally twice daily, days 1-15 (morning dose) Drug: RO5185426 960 mg orally twice daily, from day 22 onward |
Experimental: 3 |
Drug: RO5185426
dosage c) orally twice daily, days 1-15 (morning dose) Drug: RO5185426 960 mg orally twice daily, from day 22 onward |
Experimental: 4 |
Drug: RO5185426
dosage d) orally twice daily, days 1-15 (morning dose) Drug: RO5185426 960 mg orally twice daily, from day 22 onward |
- 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 ]
- 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 ]
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 ]
- 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 ]
- 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 ]
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9 [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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.
- 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).
- 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.
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01107418
United States, California | |
La Jolla, California, United States, 92093 | |
San Francisco, California, United States, 94115 | |
Stanford, California, United States, 94305 | |
United States, Connecticut | |
New Haven, Connecticut, United States, 06510-3289 | |
United States, Illinois | |
Chicago, Illinois, United States, 60637 | |
Park Ridge, Illinois, United States, 60068 | |
United States, Iowa | |
Sioux City, Iowa, United States, 51101 | |
United States, Nebraska | |
Omaha, Nebraska, United States, 68114 | |
United States, Ohio | |
Columbus, Ohio, United States, 43219 | |
United States, Rhode Island | |
East Providence, Rhode Island, United States, 02915 | |
United States, Virginia | |
Charlottesville, Virginia, United States, 22908 | |
Australia, South Australia | |
Adelaide, South Australia, Australia, 5000 | |
Australia, Victoria | |
Melbourne, Victoria, Australia, 3181 |
Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Hoffmann-La Roche |
ClinicalTrials.gov Identifier: | NCT01107418 |
Other Study ID Numbers: |
NP25163 |
First Posted: | April 21, 2010 Key Record Dates |
Results First Posted: | August 26, 2015 |
Last Update Posted: | August 26, 2015 |
Last Verified: | July 2015 |
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |