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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

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ClinicalTrials.gov Identifier: NCT01264380
Recruitment Status : Completed
First Posted : December 21, 2010
Results First Posted : December 17, 2015
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignant Melanoma Drug: RO5185426 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : January 2011
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: 1 Drug: RO5185426
Single oral dose, fasted
Experimental: 2 Drug: RO5185426
Single oral dose, with high fat meal
Experimental: C Drug: RO5185426
Continuous administration, orally twice daily


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


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

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
Contacts and Locations
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Information from the National Library of Medicine

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): NCT01264380


Locations
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United States, California
La Jolla, California, United States, 92037
Los Angeles, California, United States, 90095-1752
San Francisco, California, United States, 94115-1705
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01264380     History of Changes
Other Study ID Numbers: NP25396
First Posted: December 21, 2010    Key Record Dates
Results First Posted: December 17, 2015
Last Update Posted: November 2, 2016
Last Verified: November 2016
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas