Phase I Trial of RO5126766 (DDU RAF/MEK)
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|ClinicalTrials.gov Identifier: NCT02407509|
Recruitment Status : Unknown
Verified March 2015 by Royal Marsden NHS Foundation Trust.
Recruitment status was: Recruiting
First Posted : April 3, 2015
Last Update Posted : April 3, 2015
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumours Multiple Myeloma||Drug: RO5126766||Phase 1|
This is a single centre Phase I trial evaluating two intermittent dosing schedules.
Part I: A total of six patients will be enrolled to each dosing schedule and based on assessment of toxicity, PK and PD data the optimal schedule will be taken forward into Part II (see below).
Patients will be treated on a 4-weekly cycle with a single daily dose of 4 mg of RO5126766 on either the twice weekly (Monday & Thursday) or three times weekly (Monday, Wednesday and Friday) schedule. Six patients will be enrolled per arm and after all patients have received at least one cycle of treatment, safety data and available PK/PD data will be reviewed by the Safety Review Committee (SRC). On the basis of the previous Phase I trial, dose limiting toxicities (DLTs) are not expected at a dose of 4 mg but in the event of ≥ 2 DLT's occurring in (a) the 2 x weekly arm, then no further patients will recruited into that arm and the schedule will not be taken forward to Part II, or (b) the 3 x weekly arm, a single dose reduction to 3.2mg on the same dosing schedule will be implemented and 6 patients enrolled at the reduced dose. If 4 mg given 3 x weekly is considered non-tolerable then the SRC may decide to enrol patients to the 3.2 mg dose level in the absence of dose limiting toxicity.
Selection of the optimum schedule from Part I will be made by the Safety Review Committee and will be the schedule that delivers the highest, tolerable, cumulative weekly dose. Therefore selection will be as follows:
- If both the 2 x weekly (Mon & Thurs) and 3 x weekly (Mon, Wed & Fri) schedule are tolerated at 4 mg i.e. < 2 DLT's out of a 6 patients in each schedule, then the 3 x weekly schedule will be selected.
- If the 3 x weekly schedule requires a dose reduction to 3.2 mg and the 2 x weekly schedule is tolerated at 4 mg then PD data will be evaluated relative to AUC to aid the selection.
- If ≥2 DLT's occur out of 6 patients in both schedules (despite the 3 x weekly arm being dose reduced), Part II will not be initiated and the study will be terminated.
Part II: Once the optimal dosing schedule has been established 20 patients with either solid tumours or multiple myeloma with documented KRAS, NRAS or BRAF mutations will be enrolled.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of RO5126766 (a Dual RAF/MEK Inhibitor) Exploring Intermittent, Oral Dosing Regimens in Patients With Solid Tumours or Multiple Myeloma|
|Study Start Date :||May 2013|
|Estimated Primary Completion Date :||December 2015|
|Estimated Study Completion Date :||June 2016|
Experimental: Twice weekly
RO5126766 will be administered initially as a single daily dose of 4mg using a twice weekly dosing schedule. A cycle of treatment will comprise 28 days.
Experimental: Three times weekly
RO5126766 will be administered initially as a single daily dose of 4mg using a 3 times per week dosing schedule. A cycle of treatment will comprise 28 days.
- Safety & Toxicity Profile (adverse event and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.) [ Time Frame: 1 cycle (28 days) ]
The schedule at which no more than one patient out of six patients experience a highly probable or probable drug-related dose limiting toxicity.
Causality of each adverse event to RO5126766 and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
- Pharmacokinetic Profile (Cmax/ AUC/ T½ and accumulation index) [ Time Frame: duration of study (18 months) ]Cmax/ AUC/ T½ and accumulation index of RO5126766 given via intermittent dosing schedules
- Pharmacodynamic Profile (The relationship between RO5126766 plasma concentration and pERK levels in PBMCs) [ Time Frame: duration of study (18 months) ]The relationship between RO5126766 plasma concentration and pERK levels in PBMCs
- Anti-tumour Activity ( Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) [ Time Frame: duration of study (18 months) ]Any response (stable disease, partial response or complete response) in any of the patients as determined by the Response Evaluation Criteria in Solid Tumours (RECIST version 1.1).
- Pharmacodynamics Studies in optional pre- and post-treatment paired tumour biopsy samples [ Time Frame: duration of study (18 months) ]Pharmacodynamic studies in optional pre- and post-treatment paired tumour biopsy samples.
- Exploratory Functional Imaging Studies [ Time Frame: duration of study (18 months) ]Exploratory functional imaging studies with diffusion-weighted (DW)-MRI, 1H-MRS (Magnetic Resonance Spectroscopy) and 18F-choline positron emission tomography (PET) for predictive imaging biomarkers of response.
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): NCT02407509
|Contact: Alison Turner, PhD||+44(0)20 8661 email@example.com|
|Contact: Hasina Hassam, LLB||+44(0)20 8722 firstname.lastname@example.org|
|Royal Marsden NHS Foundation Trust||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Contact: Udai Banerji, MBBS, PhD|
|Principal Investigator:||Udai Banerji, MBBS, PhD||he Institute of Cancer Research, Royal Marsden NHS Foundation Trust|