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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
Not applicable
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
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2016
Sample size
Target
Accrual to date
Final
109
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]

Results are available at https://clinicaltrials.gov/study/NCT00405587