Phase 1
Completed N=46
A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma
Source: ClinicalTrials.gov NCT01910181 ↗Enrolled (actual)
46
Serious AEs
6.5%
Results posted
Jun 2016
Primary outcomePrimary: Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 — 37.54 h*μg/mL
Summary
This open-label, multicenter study will evaluate the pharmacokinetics, safety and efficacy of vemurafenib in Chinese participants with BRAF V600 mutation-positive unresectable or metastatic melanoma. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until disease progression or unacceptable toxicity occurs.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 |
37.54 | — |
| PRIMARY AUC of RO5185426 From 0 to 8 Hours on Day 21 |
501.28 | — |
| PRIMARY AUC of RO5185426 From 0 to 12 Hours on Day 1 |
57.51 | — |
| PRIMARY AUC of RO5185426 From 0 to 12 Hours on Day 21 |
720.31 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1 |
6.93 | — |
| PRIMARY Cmax of RO5185426 Following Day 21 Dose |
77.55 | — |
| PRIMARY Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1 |
4.97 | — |
| PRIMARY Tmax of RO5185426 Following Day 21 Dose |
1.00 | — |
| PRIMARY AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose |
4328.15 | — |
| PRIMARY Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose |
35.56 | — |
| PRIMARY Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15 |
63.000 | — |
| PRIMARY Ctrough of RO5185426 on Day 19 |
65.595 | — |
| PRIMARY Ctrough of RO5185426 on Day 21 |
72.583 | — |
| PRIMARY Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1 |
17.9 | — |
| PRIMARY Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21 |
0.02 | — |
| SECONDARY Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
52.2 | — |
| SECONDARY Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1 |
54.2 | — |
| SECONDARY Duration of Response According to RECIST Version 1.1 |
9.13 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1 |
69.6 | — |
| SECONDARY Progression-Free Survival (PFS) |
8.25 | — |
| SECONDARY Percentage of Participants Who Died |
80.4 | — |
| SECONDARY Overall Survival (OS) |
18.7 | — |
Eligibility Criteria
Inclusion Criteria
- Chinese male or female participants, greater than or equal to (≥) 18 years of age
- Histologically confirmed metastatic melanoma (surgically unresectable Stage IIIC or Stage IV, American Joint Committee on Cancer)
- Treatment-naïve or having received prior systemic treatments for metastatic melanoma
- Positive BRAF V600 mutation result determined by a designated laboratory using the Cobas 4800 BRAF V600 Mutation Test
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Previous allowed chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to study drug administration, and all associated toxicity must be resolved (to less than or equal to [≤] Grade 1 or baseline)
- Recovery from effects of any major surgery (excluding tumor biopsy at baseline) or significant traumatic injury at least 14 days before the first dose of study treatment
- Adequate hematologic, renal, and liver function as defined by protocol
- Fertile men and women must use an effective method of contraception during treatment and for ≥6 months after completion of treatment as directed by their physician (in accordance with local requirements).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy greater than (>) 3 months
- Able to swallow pills
Exclusion Criteria
- Active central nervous system (CNS) lesions (radiographically unstable/symptomatic lesions), except participants treated with stereotactic therapy or surgery who remain without evidence of disease progression in brain for ≥3 months and have been off corticosteroid and anticonvulsant therapy for ≥3 weeks
- History of or known spinal cord compression or carcinomatous meningitis
- Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
- Active squamous cell carcinoma (SCC) that has not been excised or has not yet adequately healed post excision
- Pregnant or lactating women
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate vemurafenib absorption
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic attack, or symptomatic pulmonary embolism
- Known clinically significant active infection
- History of allogeneic bone marrow transplantation or organ transplantation
- Previous malignancy within the past 5 years other than adequately treated basal cell carcinoma or SCC of the skin, melanoma in-situ, and carcinoma in-situ of the cervix and/or curatively treated cancer from which the participant is currently disease-free, or any malignancy from which the participant has been continuously disease-free for at least 5 years
- Previous treatment with a BRAF inhibitor (sorafenib allowed) or MEK inhibitor
- Participants who have had one or more doses of vemurafenib in a previous clinical trial
- Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS)-related illness, or hepatitis B virus or hepatitis C virus (HCV) carriers (hepatitis B surface antigen-positive, HCV antibody-positive)
- Received any investigational treatment within 4 weeks of study drug start
Data sourced from ClinicalTrials.gov (NCT01910181). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.