NeoplasmsPhase 1NCT01143753
A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors
A Phase 1 study testing RO5212054 in people with Neoplasms, run by Hoffmann-La Roche at 5 sites in 3 countries.
Trial summary
This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- RO5212054
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 27 Jul 2010to 2 May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced solid tumor
- Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate liver, renal and bone marrow function
Who cannot join
- Participants for whom standard therapy exists and is considered appropriate by the investigator
- Prior treatment with an inhibitor of BRAF (sorafenib allowed)
- Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
- Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
- Anticipated or ongoing anti-cancer therapies other than those administered in this study
- Serious cardiovascular illness within the 6 months prior to study drug administration
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Australia3 sites
Royal Adelaide Hospital; Oncology
Adelaide, South Australia, 5000
Austin Hospital; Medical Oncology
Heidelberg, Victoria, 3084
Royal Melbourne Hospital; Hematology and Medical Oncology
Parkville, Victoria, 3052
About this study
Official title: An Open-Label, Multiple Ascending Dose (MAD) Study of the Selective BRAF Inhibitor RO5212054 (PLX3603) to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With BRAF V600-Mutated Advanced Solid Tumours
This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
- Conditions
- Neoplasms
- Being tested
- RO5212054
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO5212054Drug
Also called PLX3603
Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned.
| Study group | Role | What they receive |
|---|---|---|
| RO5212054: Continuous Dosing Cohort | Experimental | Participants will receive RO5212054 in escalating dose levels. Receives: Drug: RO5212054 |
| RO5212054: New Formulation (F05) Bridging Cohort | Experimental | Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort. Receives: Drug: RO5212054 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose Limiting Toxicity
Measured: Baseline up to 21 days
Maximal Tolerated Dose of RO5212054
Measured: Baseline up to 21 days
Maximum Plasma Concentration of RO5212054
Detailed timeframe:
Pre-dose (0 hour [hr]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Measured: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Time to Reach Maximum Plasma Concentration of RO5212054
Detailed timeframe:
Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Measured: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Area Under The Plasma Concentration-Time Curve of RO5212054
Detailed timeframe:
Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Measured: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Secondary outcomes (1)
Percentage of Participants With Adverse Events
Measured: Baseline up to approximately 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2010 (estimated)
- Study start27 Jul 2010
- Primary completion30 Jun 2012
- Study completion2 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01143753
- Sponsor's protocol ID
- NP25247
- Other IDs
- 2010-018330-42
- Status last verified
- Jul 2017
- First submitted
- 11 Jun 2010
- Last updated
- 28 Jul 2017
- Results posted
- No
Publications
Dienstmann R, Lassen U, Cebon J, Desai J, Brown MP, Evers S, Su F, Zhang W, Boisserie F, Lestini B, Schostack K, Meresse V, Tabernero J. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2016 Apr;11(2):149-56. doi: 10.1007/s11523-015-0381-x.
PubMed 26310975
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multiple Ascending Dose (MAD) Study of the Selective BRAF Inhibitor RO5212054 (PLX3603) to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With BRAF V600-Mutated Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT01143753
- Acronym / sponsor ID
- NP25247
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2010 (actual)
- Primary completion
- 30 Jun 2012 (actual)
- Study completion
- 2 May 2017 (actual)
- First posted
- 14 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RO5212054: Continuous Dosing Cohort | Experimental | Drug: RO5212054Participants will receive RO5212054 in escalating dose levels. |
| RO5212054: New Formulation (F05) Bridging Cohort | Experimental | Drug: RO5212054Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Advanced solid tumor
- Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate liver, renal and bone marrow function
Key exclusion criteria (6 listed)
- Participants for whom standard therapy exists and is considered appropriate by the investigator
- Prior treatment with an inhibitor of BRAF (sorafenib allowed)
- Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
- Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
- Anticipated or ongoing anti-cancer therapies other than those administered in this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO5212054Also: PLX3603Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned. | Drug | RO5212054: Continuous Dosing Cohort, RO5212054: New Formulation (F05) Bridging Cohort |
Primary outcome
Percentage of Participants With Dose Limiting Toxicity
Time frame: Baseline up to 21 days
Maximal Tolerated Dose of RO5212054
Time frame: Baseline up to 21 days
Maximum Plasma Concentration of RO5212054
Time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hour [hr]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Time to Reach Maximum Plasma Concentration of RO5212054
Time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Area Under The Plasma Concentration-Time Curve of RO5212054
Time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
1 secondary outcome
Percentage of Participants With Adverse Events
Time frame: Baseline up to approximately 7 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Derived from this study: PubMed 26310975Dienstmann R, Lassen U, Cebon J, Desai J, Brown MP, Evers S, Su F, Zhang W, Boisserie F, Lestini B, Schostack K, Meresse V, Tabernero J. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2016 Apr;11(2):149-56. doi: 10.1007/s11523-015-0381-x.
Related trials for Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO5212054 in people with Neoplasms, run by Hoffmann-La Roche at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia, Denmark, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Dose Limiting Toxicity (time frame: Baseline up to 21 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01143753, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2017; AzTrials last refreshed its copy on 7 Nov 2026.