Metastatic MelanomaPhase 1/2CHIR-265-MEL01NCT00304525
A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma
A Phase 1/2 study testing RAF265 in people with Metastatic Melanoma, run by Novartis Pharmaceuticals at 11 sites in 2 countries.
Trial summary
The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of RAF265 in patients with locally advanced and metastatic melanoma. Phase II portion of study (dose expansion) has been cancelled with Amendment 7 as of Dec 2011. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- RAF265
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Apr 2006to Nov 2013
- Phase
- Phase 1/2
- 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
- Confirmed diagnosis of melanoma, locally advanced AJCC Stage IIIB to metastatic Stage IV
- Measurable disease - at least one lesion measured in at least one dimension as ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan
- ECOG performance status of 0 or 1
- No concurrent anticancer or investigational therapy for at least 4 weeks prior to enrollment
- No major surgery for at least 4 weeks prior to enrollment
Who cannot join
- Significant cardiac disease or other significant medical/psychiatric disease
- History of primary central nervous system tumor or brain metastases
- History of melena, hematemesis, or hemoptysis within the last 3 months
- Previous therapy with certain molecularly targeted agents
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Georgia Regents University Cancer Clinical Research Unit
Augusta, Georgia, 30912
University of Colorado Univ.ofColoradoCancerCenter
Aurora, Colorado, 80045
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
Baltimore, Maryland, 21231
Massachusetts General Hospital Dept of Cancer for Melanoma
Boston, Massachusetts, 02114
Dana Farber Cancer Institute DFCI
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center Dept.ofBethIsraelDeaconess(3)
Boston, Massachusetts, 02215
University of Texas/MD Anderson Cancer Center Onc. Dept,
Houston, Texas, 77030-4009
Vanderbilt University Medical Center Dept. of Cancer Center
Nashville, Tennessee, 37232
University of Pennsylvania Health System Dept of Hospital of UnivofPenn
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Cancer Institute Dept of Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase I/II, Open-label, Dose Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RAF265 (CHIR-265)Administered Orally to Patients With Locally Advanced or Metastatic Melanoma.
The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of RAF265 in patients with locally advanced and metastatic melanoma.
Phase II portion of study (dose expansion) has been cancelled with Amendment 7 as of Dec 2011.
Read the detailed description
The Ras/Raf/MEK/ERK pathway plays a prominent role in controlling several key cellular functions including growth, proliferation and survival. B-Raf is a member of the Ras/Raf/MEK/ERK pathway and is frequently mutated in melanoma resulting in activation of the MAPK pathway. RAF265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.
The primary objectives of this study are to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and the safety profile of RAF265 when administered orally to subjects with locally advanced or metastatic melanoma; to determine the plasma pharmacokinetics (PKs) of orally administered RAF265; and to evaluate potential pharmacodynamic effects of RAF265 using tumor biopsies, peripheral blood samples, and tumor imaging.
- Conditions
- Metastatic Melanoma
- Being tested
- RAF265
- Keywords
- Anti-angiogenesis therapy, Kinase inhibitor therapy, Raf inhibitor, Locally Advanced Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAF265Drug
A liquid nonaqueous oral formulation. Switched to a tablet formulations with was 60% bioavailable, relative to the liquid at 50mg dose. The liquid dose will be multiplied by a factor of 1.67 to achieve a comparable tablet dose. Tablets are available in 10mg and 50mg strengths.
| Study group | Role | What they receive |
|---|---|---|
| RAF265 - Arm 1 | Experimental | Patients received 10mg RAF265 as a once weekly dose until progressive disease was confirmed. Receives: Drug: RAF265 |
| RAF265 - Arm 2 | Experimental | RAF265 is given as a single "PK run-in" dose, a single loading dose on day 1 of cycle 1, followed by once daily maintenance doses. Receives: Drug: RAF265 |
| RAF265 - Arm 3 | Experimental | Patients were treated with once weekly dosing of RAF265 Receives: Drug: RAF265 |
| RAF265 - Arm 4 | Experimental | Patients with locally advanced or metastatic melanoma will utilize a dose close to or at the MTD/RPTD of the liquid formulation that was determined in Arm 2. Receives: Drug: RAF265 |
| RAF265 - Arm 5 | Experimental | RAF265 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week. Receives: Drug: RAF265 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Measured: at the end of dose escalation
Dose limiting toxicities
Measured: during the PK run-in phase and first cycle (28 day cycle)
Safety profile
Measured: throughout the study
Evaluate potential pharmacodynamic effects
Measured: throughout the study
Pharmacokinetic profile
Measured: throughout the study
Secondary outcomes (3)
Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response
Measured: throughout the study
Determine the response rate for BRAF mutant patients
Measured: Every 2 months
Determine the recommended phase two dose
Measured: at the end of dose escalation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2006 (estimated)
- Study startApr 2006
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsNovartis Pharmaceuticals, Study director, Novartis Pharmeceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00304525
- Sponsor's protocol ID
- CRAF265A2101
- Other IDs
- 2007-005367-10
- Acronym
- CHIR-265-MEL01
- Status last verified
- Aug 2020
- First submitted
- 17 Mar 2006
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-label, Dose Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RAF265 (CHIR-265)Administered Orally to Patients With Locally Advanced or Metastatic Melanoma.
- ClinicalTrials.gov ID
- NCT00304525
- Acronym / sponsor ID
- CHIR-265-MEL01 / CRAF265A2101
- Conditions
- Metastatic Melanoma
- Keywords
- Anti-angiogenesis therapy, Kinase inhibitor therapy, Raf inhibitor, Locally Advanced Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2006
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 20 Mar 2006 (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.
The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of RAF265 in patients with locally advanced and metastatic melanoma.
Phase II portion of study (dose expansion) has been cancelled with Amendment 7 as of Dec 2011.
Detailed description
The Ras/Raf/MEK/ERK pathway plays a prominent role in controlling several key cellular functions including growth, proliferation and survival. B-Raf is a member of the Ras/Raf/MEK/ERK pathway and is frequently mutated in melanoma resulting in activation of the MAPK pathway. RAF265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.
The primary objectives of this study are to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and the safety profile of RAF265 when administered orally to subjects with locally advanced or metastatic melanoma; to determine the plasma pharmacokinetics (PKs) of orally administered RAF265; and to evaluate potential pharmacodynamic effects of RAF265 using tumor biopsies, peripheral blood samples, and tumor imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| RAF265 - Arm 1 | Experimental | Drug: RAF265Patients received 10mg RAF265 as a once weekly dose until progressive disease was confirmed. |
| RAF265 - Arm 2 | Experimental | Drug: RAF265RAF265 is given as a single "PK run-in" dose, a single loading dose on day 1 of cycle 1, followed by once daily maintenance doses. |
| RAF265 - Arm 3 | Experimental | Drug: RAF265Patients were treated with once weekly dosing of RAF265 |
| RAF265 - Arm 4 | Experimental | Drug: RAF265Patients with locally advanced or metastatic melanoma will utilize a dose close to or at the MTD/RPTD of the liquid formulation that was determined in Arm 2. |
| RAF265 - Arm 5 | Experimental | Drug: RAF265RAF265 was administered as a continuous dose for 2 weeks followed by a dose holiday of 1 week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of melanoma, locally advanced AJCC Stage IIIB to metastatic Stage IV
- Measurable disease - at least one lesion measured in at least one dimension as ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan
- ECOG performance status of 0 or 1
- No concurrent anticancer or investigational therapy for at least 4 weeks prior to enrollment
- No major surgery for at least 4 weeks prior to enrollment
Key exclusion criteria (4 listed)
- Significant cardiac disease or other significant medical/psychiatric disease
- History of primary central nervous system tumor or brain metastases
- History of melena, hematemesis, or hemoptysis within the last 3 months
- Previous therapy with certain molecularly targeted agents
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 |
|---|---|---|
| RAF265A liquid nonaqueous oral formulation. Switched to a tablet formulations with was 60% bioavailable, relative to the liquid at 50mg dose. The liquid dose will be multiplied by a factor of 1.67 to achieve a comparable tablet dose. Tablets are available in 10mg and 50mg strengths. | Drug | RAF265 - Arm 1, RAF265 - Arm 2, RAF265 - Arm 3, RAF265 - Arm 4, RAF265 - Arm 5 |
Primary outcome
Maximum tolerated dose
Time frame: at the end of dose escalation
Dose limiting toxicities
Time frame: during the PK run-in phase and first cycle (28 day cycle)
Safety profile
Time frame: throughout the study
Evaluate potential pharmacodynamic effects
Time frame: throughout the study
Pharmacokinetic profile
Time frame: throughout the study
3 secondary outcomes
Evaluate whether somatic mutations in BRAF and N-RAS genes are associated with modulation of pharmacodynamic markers and clinical response
Time frame: throughout the study
Determine the response rate for BRAF mutant patients
Time frame: Every 2 months
Determine the recommended phase two dose
Time frame: at the end of dose escalation
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 19 Dec 2020.
- CRAF265A2101 Results at Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
Novartis Pharmaceuticals study director
Novartis Pharmeceuticals
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RAF265 in people with Metastatic Melanoma, run by Novartis Pharmaceuticals at 11 sites in 2 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 5 inclusion and 4 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Switzerland. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Maximum tolerated dose (time frame: at the end of dose escalation). 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?
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 19 Dec 2020.