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NCT Number: NCT01264380

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis 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

La Jolla, California, United States

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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 IV, American Joint Committee on Cancer)
  • Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
  • Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Evaluable disease (measurable for disease progression according to RECIST criteria)
  • Adequate hematological, renal and liver function

Exclusion criteria

  • Active CNS lesions
  • 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
  • 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
  • Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  • Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug

Treatment and study plan

RO5185426

Drug

Single oral dose, fasted

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.

  2. Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    PK analyses was performed after the completion of Period A and Period B of this study for all participants.

  3. Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    PK analyses was performed after the completion of Period A and Period B of this study for all participants.

  4. Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States

    Time frame: Pre-dose on Periods A and B

    Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

  5. Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    PK analyses was performed after the completion of Period A and Period B of this study for all participants.

  6. Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

  7. Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States

    Time frame: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

    Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Secondary outcomes

  1. Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)

    Time frame: From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124)

    BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  2. Overall Survival (OS)

    Time frame: From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124)

    OS was defined as the time, in months, from the date of the first study drug 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, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Dec 21, 2010
Registry last updated
Nov 2, 2016

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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