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Completed

NCT Number: NCT01910181

A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma

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.

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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

Beijing Cancer Hospital, Beijing, China

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Who can participate

Healthy volunteers accepted: No

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

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

Treatment and study plan

Vemurafenib

Drug

Participants will receive vemurafenib at a dose of 960 mg twice daily orally.

Other names: Zelboraf

Primary outcomes

  1. Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in hours by micrograms per milliliter (h*μg/mL).

  2. AUC of RO5185426 From 0 to 8 Hours on Day 21

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL.

  3. AUC of RO5185426 From 0 to 12 Hours on Day 1

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL.

  4. AUC of RO5185426 From 0 to 12 Hours on Day 21

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL.

  5. Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1

    Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in micrograms per milliliter (μg/mL).

  6. Cmax of RO5185426 Following Day 21 Dose

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

    Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in μg/mL.

  7. Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1

    Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours.

  8. Tmax of RO5185426 Following Day 21 Dose

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

    Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours.

  9. AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 168 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL.

  10. Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

    Plasma PK samples were obtained from each participant for calculation of t1/2, defined as the time elapsed for plasma concentrations to drop by half. The value was averaged among all participants and expressed in hours.

  11. Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15

    Time frame: Pre-dose (0 hours) on Day 15

    Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL.

  12. Ctrough of RO5185426 on Day 19

    Time frame: Pre-dose (0 hours) on Day 19

    Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL.

  13. Ctrough of RO5185426 on Day 21

    Time frame: Pre-dose (0 hours) on Day 21

    Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL.

  14. Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21

    Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The AUC on Day 21 was divided by the AUC for Day 1. The resulting value was averaged among all participants and expressed as the accumulation ratio.

  15. Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21

    Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

    Plasma PK samples were obtained from each participant and the kel was estimated. The value was averaged among all participants and expressed in inverse hours (h^-1).

Secondary outcomes

  1. 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

    Time frame: 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)

    Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease from Baseline in sum diameter of target lesions. The percentage of participants with a best overall response of CR or PR during the study was reported.

  2. Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1

    Time frame: 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)

    Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants who died or progressed after CR or PR was reported.

  3. Duration of Response According to RECIST Version 1.1

    Time frame: 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)

    Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). Duration of response was defined as the time from initial response of CR or PR to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% confidence interval (CI) was estimated using the Brookmeyer-Crowley method.

  4. Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1

    Time frame: 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)

    Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants with death or disease progression during the study was reported.

  5. Progression-Free Survival (PFS)

    Time frame: 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)

    Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). PFS was defined as the time from treatment start to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method.

  6. Percentage of Participants Who Died

    Time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study

    The percentage of participants who died during the study was reported.

  7. Overall Survival (OS)

    Time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study

    OS was defined as the time from treatment start to death from any cause. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2013
Study completion
2018
First posted
Jul 29, 2013
Registry last updated
May 29, 2019

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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