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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00405587




Registration number
NCT00405587
Ethics application status
Date submitted
28/11/2006
Date registered
30/11/2006
Date last updated
22/08/2017

Titles & IDs
Public title
Safety Study of PLX4032 in Patients With Solid Tumors
Scientific title
A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors
Secondary ID [1] 0 0
PLX06-02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Colorectal Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PLX4032

Experimental: PLX4032 - Open-label, sequential dose escalation


Treatment: Drugs: PLX4032
Oral capsules administered BID

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Timepoint [1] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [2] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Timepoint [2] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [3] 0 0
Peak Concentration (Cmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Timepoint [3] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [4] 0 0
Peak Concentration (Cmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Timepoint [4] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose on Day 15, pre-morning dose on Day 16
Primary outcome [5] 0 0
Time to Peak Concentration (Tmax) of RO5185426 on Day 1 - Dose Escalation: Original Formulation
Timepoint [5] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [6] 0 0
Time to Peak Concentration (Tmax) of RO5185426 on Day 15 - Dose Escalation: Original Formulation
Timepoint [6] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, pre-morning dose on Day 16
Primary outcome [7] 0 0
AUC of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Timepoint [7] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [8] 0 0
AUC of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Timepoint [8] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [9] 0 0
Mean RO5185426 Accumulation Ratios - Dose Escalation: MBP Formulation
Timepoint [9] 0 0
Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Primary outcome [10] 0 0
Mean RO5185426 Accumulation Ratios - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Timepoint [10] 0 0
Day 1 and Day 15: pre-morning dose and at 0.5, 1, 2, 4, and 8 hours post-morning dose
Primary outcome [11] 0 0
Cmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Timepoint [11] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [12] 0 0
Cmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Timepoint [12] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Primary outcome [13] 0 0
Tmax of RO5185426 on Day 1 - Dose Escalation: MBP Formulation
Timepoint [13] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [14] 0 0
Tmax of RO5185426 on Day 15 - Dose Escalation: MBP Formulation
Timepoint [14] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Primary outcome [15] 0 0
AUC of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Timepoint [15] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [16] 0 0
AUC of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Timepoint [16] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Primary outcome [17] 0 0
Cmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Timepoint [17] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [18] 0 0
Cmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- Positive CRC
Timepoint [18] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15 and pre-morning dose on Day 16
Primary outcome [19] 0 0
Tmax of RO5185426 on Day 1 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Timepoint [19] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1, pre-morning dose on Day 2 and Day 8
Primary outcome [20] 0 0
Tmax of RO5185426 on Day 15 - Extension: BRAFV600E- Positive Melanoma and BRAFV600E- CRC
Timepoint [20] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 15, and pre-morning dose on Day 16
Primary outcome [21] 0 0
Percentage of Participants With a Confirmed and an Unconfirmed Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST Version (v) 1.0 - Extension: BRAFV600E- Positive Melanoma
Timepoint [21] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Primary outcome [22] 0 0
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Extension: BRAFV600E- Positive CRC
Timepoint [22] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Primary outcome [23] 0 0
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: Original Formulation
Timepoint [23] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Primary outcome [24] 0 0
Percentage of Participants With BOR of CR or PR According to RECIST v1.0 - Dose Escalation: MBP Formulation
Timepoint [24] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Secondary outcome [1] 0 0
Duration of CR or PR Using RECIST v 1.0 - Extension BRAFV600E- Positive Melanoma
Timepoint [1] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 337 days)
Secondary outcome [2] 0 0
Percentage of Participants With Progression-Free Survival (PFS) Using RECIST v 1.0 - Melanoma Extension Cohort
Timepoint [2] 0 0
Month 1, 3, 4, 6, 9, and Last event (350) days
Secondary outcome [3] 0 0
PFS Using RECIST v1.0 - Extension BRAFV600E Positive Melanoma
Timepoint [3] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to data cutoff (up to 421 days)
Secondary outcome [4] 0 0
Percentage of Participants Who Died - Extension: BRAFV600E- Positive Melanoma
Timepoint [4] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Secondary outcome [5] 0 0
Overall Survival (OS) - Extension: BRAFV600E- Positive Melanoma
Timepoint [5] 0 0
Screening, BL, until PD, or end of efficacy follow-up, up to 444 days
Secondary outcome [6] 0 0
Time to CR or PR Using RECIST v1.0 - Extension: BRAFV600E- Positive Melanoma
Timepoint [6] 0 0
Screening, BL, and up to 168 days
Secondary outcome [7] 0 0
Mean Dose-Normalized Steady-State AUC of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
Timepoint [7] 0 0
Pre-morning dose and at 0.5, 1, 2, 4, and 8, and 24 hours post-morning dose
Secondary outcome [8] 0 0
Mean Dose-Normalized Steady-State Cmax of RO5185426 80 mg and 120 mg Capsules - Dose Escalation: MBP Formulation and Extension: BRAFV600E- Positive Melanoma
Timepoint [8] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2 and Day 8, and Day 16
Secondary outcome [9] 0 0
Decrease in Tumor Uptake of 18F-fluorodeoxyglucose (FDG)
Timepoint [9] 0 0
BL and Day 15
Secondary outcome [10] 0 0
Cmax of RO5185426 - Food Effect
Timepoint [10] 0 0
Pre-morning dose, 0.5, 1, 2, 4, and 8 hour post-morning dose on Day 1 and 15, pre-morning dose on Day 2, Day 8, and Day 16
Secondary outcome [11] 0 0
Tumor Levels of Phosphorylated Extracellular Signal-Regulated Kinapse (ERK), Cyclin D1, and Ki-67
Timepoint [11] 0 0
BL and Day 15

Eligibility
Key inclusion criteria
* Solid tumors confirmed histologically whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist
* Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032
* Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved prior to administration of PLX4032
* Patients in the Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay
* ECOG performance status 0 or 1
* Life expectancy = 3 months
* Adequate hematologic, hepatic, and renal function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Brain metastases that are progressing or have been documented to be stable for less than 3 months, or for which systemic corticosteroids are required
* Investigational drug use within 28 days of the first dose of PLX4032
* Uncontrolled intercurrent illness
* Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Plexxikon
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Roche Pharma AG
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Henry Hsu, MD
Address 0 0
Plexxikon
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur ... [More Details]