Clinical trial NCT01910181: A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma
Official title: A Phase I Open-Label, Multicenter, Multiple-Dose Study to Investigate the Pharmacokinetics, Safety, and Efficacy of Vemurafenib in Chinese Patients With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-07-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1
measure: AUC of RO5185426 From 0 to 8 Hours on Day 21
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21
measure: AUC of RO5185426 From 0 to 12 Hours on Day 1
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
measure: AUC of RO5185426 From 0 to 12 Hours on Day 21
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21
measure: Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
measure: Cmax of RO5185426 Following Day 21 Dose
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
measure: Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
measure: Tmax of RO5185426 Following Day 21 Dose
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
measure: AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
measure: Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
measure: Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15
timeFrame: Pre-dose (0 hours) on Day 15
measure: Ctrough of RO5185426 on Day 19
timeFrame: Pre-dose (0 hours) on Day 19
measure: Ctrough of RO5185426 on Day 21
timeFrame: Pre-dose (0 hours) on Day 21
measure: Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21
measure: Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21
timeFrame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Secondary outcomes:
measure: 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
timeFrame: Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression (up to 16 months as of data cutoff 15-Dec-2014)
measure: Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1
timeFrame: Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)
measure: Duration of Response According to RECIST Version 1.1
timeFrame: Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)
measure: Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1
timeFrame: Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)
measure: Progression-Free Survival (PFS)
timeFrame: Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)
measure: Percentage of Participants Who Died
timeFrame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study
measure: Overall Survival (OS)
timeFrame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yet-sen University Cancer Center
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Si L, Zhang X, Xu Z, Jiang Q, Bu L, Wang X, Mao L, Zhang W, Richie N, Guo J. Vemurafenib in Chinese patients with BRAFV600 mutation-positive unresectable or metastatic melanoma: an open-label, multicenter phase I study. BMC Cancer. 2018 May 3;18(1):520. doi: 10.1186/s12885-018-4336-3.