Advanced BRAF-mutant CancersPhase 1/2NCT01616199
Study of PX-866 and Vemurafenib in Patients With Advanced Melanoma
A Phase 1/2 study testing PX-866 and vemurafenib in people with Advanced BRAF-mutant Cancers, run by Cascadian Therapeutics Inc. at 5 sites in United States.
Trial summary
The purpose of the phase 1 portion of the study is to determine the maximally tolerated dose (MTD) or recommended dose (RD) and the safety/tolerability of PX-866 in combination vemurafenib in patients with any advanced BRAF-mutant cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced BRAF-mutant Cancers
- What is being tested?
- PX-866 and vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2012to Mar 2015
- 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
- ≥ 18 years at time of consent
- If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug
- If female of child-bearing potential, negative pregnancy test
- For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. Patients must have disease sites amenable to biopsy. For Phase 2: must have histologically or cytologically-confirmed BRAF mutation-positive (V600E or V600K) advanced (defined as unresectable Stage IIIC or IV) melanoma that has not been treated with a selective BRAF inhibitor
- For Phase 1: must have measurable or non-measurable disease. For Phase 2: must have measurable disease per RECIST 1.1
- For Phase 1: no restriction on number of prior therapy regimens. For Phase 2: the following restrictions on prior therapy apply: 1) must not have been treated with a selective BRAF inhibitor and must not have had more than 2 prior treatment regimens for advanced metastatic disease; 2) must have completed prior cytotoxic chemotherapy a minimum of 4 weeks prior to starting PX-866 and/or vemurafenib (except for BCNU and/or mitomycin C, which must have been completed a minimum of 6 weeks prior to starting therapy). Prior biologic therapy and localized radiation therapy must have been completed a minimum of 2 weeks prior to starting therapy.
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- All toxicities related to prior cancer therapies other than alopecia must have resolved to Grade 1 or less
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- In the opinion of the clinical investigator, life expectancy > 3 months
- Adequate hematologic function
- Adequate hepatic function
- Serum creatinine < 2.0 mg/dL
- Adequate cardiac function
- Corrected QTc must be <480 milliseconds
Who cannot join
- May not be receiving any other investigational agents
- Active central nervous system (CNS) metastases are excluded. Patients with a history of CNS metastasis, who have been treated prior to enrollment, must be stable for eight weeks after completion of treatment. These patients must have undergone appropriate imaging studies and currently be on a stable, lowest possible dose of steroids
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PX-866 or vemurafenib
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Uncorrectable electrolyte abnormalities or long QT syndrome
- Poorly controlled diabetes mellitus
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- Pregnant, breastfeeding, or planning to become pregnant
- Known to be human immunodeficiency virus (HIV)-positive
- Inability to swallow pills
- Previous treatment with a phosphatidylinositol-3-kinase (PI-3K) inhibitor
- Any other significant medical or psychiatric condition that in the opinion of the investigator renders the patient inadequate for participation
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
New York University
New York, New York, 10016
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase 1/2 Study of PI-3K Inhibition With PX-866 Combined With Vemurafenib (BRAF Inhibitor) in Patients With BRAF-mutant Cancer Including Advanced Melanoma
The purpose of the phase 1 portion of the study is to determine the maximally tolerated dose (MTD) or recommended dose (RD) and the safety/tolerability of PX-866 in combination vemurafenib in patients with any advanced BRAF-mutant cancer.
The purpose of the phase 2 portion of the study is to compare progression free survival (PFS), antitumor activity (response rate), disease control rate (DCR), and the safety and tolerability of PX-866 in combination with vemurafenib vs. vemurafenib alone in patients with advanced BRAF-mutant melanoma at the doses recommended from Phase 1.
Read the detailed description
This is a Phase 1 / 2 open-label study of PX-866 given in combination with vemurafenib to patients with BRAF-mutant cancer, including advanced melanoma.
Phase 1 will use a 3+3 dose escalation design to evaluate up to three dose levels of PX-866 in combination with up to two dose levels of vemurafenib in order to identify the maximal tolerated dose/recommended dose (MTD/RD) of both PX-866 and vemurafenib to be used in Phase 2. Vemurafenib will be administered orally twice per day on days 1-28 of all cycles except cycle 1, where vemurafenib will be administered on days 9-28 to allow for PK assessments). PX-866 will be administered once per day on days 1-28 of each cycle.
Phase 2 will evaluate the antitumor activity and safety of PX-866 given to patients randomized 2:1 to receive combination with vemurafenib at the doses recommended from Phase 1 compared with vemurafenib alone administered at the approved dose orally BID. All treatments will be administered on a 28-day cycle.
Patients randomized to receive single-agent vemurafenib may cross-over to receive the combination treatment at the time of progression. Patients will be evaluated for progression approximately every 8 weeks for the initial 24 weeks and every 12 weeks thereafter. All patients with stable disease (SD) or better, will receive repeat cycles until disease progression (PD), unacceptable toxicity, or withdrawal of consent.
- Conditions
- Advanced BRAF-mutant Cancers
- Being tested
- PX-866, vemurafenib
- Keywords
- PX-866, BRAF-mutant cancers, Advanced melanoma, BRAF inhibitor, Vemurafenib, Zelboraf, PI-3K inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PX-866Drug
Also called PI-3K inhibitor
Phase 1 dose escalation: PX-866 in combination administered orally every day in 28-day cycles until progression or unacceptable toxicity.
Phase 2 combination: PX-866 and vemurafenib administered every day in 28 day cycles until progression or unacceptable toxicity.
Phase 2 single-agent: vemurafenib administered orally at labeled dose every day in 28 day cycles until progression or unacceptable toxicity.
vemurafenibDrug
Also called Zelboraf
vemurafenib is a B-Raf enzyme inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Escalation of PX-866 + vemurafenib | Experimental | PX-866 given with vemurafenib Receives: Drug: PX-866; Drug: vemurafenib |
| Phase 2 Combination PX-866 + vemurafenib | Experimental | PX-866 given with vemurafenib Receives: Drug: PX-866; Drug: vemurafenib |
| Phase 2 Single-agent vemurafenib | Active comparator | vemurafenib given as a single agent Receives: Drug: vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events (phase 1)
Measured: 28 days
Progression-free survival (PFS) (phase 2)
Measured: 56 days
Secondary outcomes (4)
Plasma concentrations of PX-866 and metabolites (phase 1)
Measured: 44 days
Objective Response Rate (ORR)(phase 2)
Measured: 56 days
Disease Control Rate (DCR)(phase 2)
Measured: 56 Days
Plasma concentrations of vemurafenib (phase 1)
Measured: 44 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2012 (estimated)
- Study startAug 2012
- Primary completionDec 2014
- Study completionMar 2015
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced BRAF-mutant CancersStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cascadian Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01616199
- Sponsor's protocol ID
- PX-866-007
- Status last verified
- Jul 2015
- First submitted
- 6 Jun 2012
- Last updated
- 16 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of PI-3K Inhibition With PX-866 Combined With Vemurafenib (BRAF Inhibitor) in Patients With BRAF-mutant Cancer Including Advanced Melanoma
- ClinicalTrials.gov ID
- NCT01616199
- Acronym / sponsor ID
- PX-866-007
- Conditions
- Advanced BRAF-mutant Cancers
- Keywords
- PX-866, BRAF-mutant cancers, Advanced melanoma, BRAF inhibitor, Vemurafenib, Zelboraf, PI-3K inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Cascadian Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 11 Jun 2012 (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 the phase 1 portion of the study is to determine the maximally tolerated dose (MTD) or recommended dose (RD) and the safety/tolerability of PX-866 in combination vemurafenib in patients with any advanced BRAF-mutant cancer.
The purpose of the phase 2 portion of the study is to compare progression free survival (PFS), antitumor activity (response rate), disease control rate (DCR), and the safety and tolerability of PX-866 in combination with vemurafenib vs. vemurafenib alone in patients with advanced BRAF-mutant melanoma at the doses recommended from Phase 1.
Detailed description
This is a Phase 1 / 2 open-label study of PX-866 given in combination with vemurafenib to patients with BRAF-mutant cancer, including advanced melanoma.
Phase 1 will use a 3+3 dose escalation design to evaluate up to three dose levels of PX-866 in combination with up to two dose levels of vemurafenib in order to identify the maximal tolerated dose/recommended dose (MTD/RD) of both PX-866 and vemurafenib to be used in Phase 2. Vemurafenib will be administered orally twice per day on days 1-28 of all cycles except cycle 1, where vemurafenib will be administered on days 9-28 to allow for PK assessments). PX-866 will be administered once per day on days 1-28 of each cycle.
Phase 2 will evaluate the antitumor activity and safety of PX-866 given to patients randomized 2:1 to receive combination with vemurafenib at the doses recommended from Phase 1 compared with vemurafenib alone administered at the approved dose orally BID. All treatments will be administered on a 28-day cycle.
Patients randomized to receive single-agent vemurafenib may cross-over to receive the combination treatment at the time of progression. Patients will be evaluated for progression approximately every 8 weeks for the initial 24 weeks and every 12 weeks thereafter. All patients with stable disease (SD) or better, will receive repeat cycles until disease progression (PD), unacceptable toxicity, or withdrawal of consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Escalation of PX-866 + vemurafenib | Experimental | Drug: PX-866, Drug: vemurafenibPX-866 given with vemurafenib |
| Phase 2 Combination PX-866 + vemurafenib | Experimental | Drug: PX-866, Drug: vemurafenibPX-866 given with vemurafenib |
| Phase 2 Single-agent vemurafenib | Active comparator | Drug: vemurafenibvemurafenib given as a single agent |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- ≥ 18 years at time of consent
- If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug
- If female of child-bearing potential, negative pregnancy test
- For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. Patients must have disease sites amenable to biopsy. For Phase 2: must have histologically or cytologically-confirmed BRAF mutation-positive (V600E or V600K) advanced (defined as unresectable Stage IIIC or IV) melanoma that has not been treated with a selective BRAF inhibitor
- For Phase 1: must have measurable or non-measurable disease. For Phase 2: must have measurable disease per RECIST 1.1
Key exclusion criteria (11 listed)
- May not be receiving any other investigational agents
- Active central nervous system (CNS) metastases are excluded. Patients with a history of CNS metastasis, who have been treated prior to enrollment, must be stable for eight weeks after completion of treatment. These patients must have undergone appropriate imaging studies and currently be on a stable, lowest possible dose of steroids
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PX-866 or vemurafenib
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Uncorrectable electrolyte abnormalities or long QT syndrome
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 |
|---|---|---|
| PX-866Also: PI-3K inhibitorPhase 1 dose escalation: PX-866 in combination administered orally every day in 28-day cycles until progression or unacceptable toxicity. Phase 2 combination: PX-866 and vemurafenib administered every day in 28 day cycles until progression or unacceptable toxicity. Phase 2 single-agent: vemurafenib administered orally at labeled dose every day in 28 day cycles until progression or unacceptable toxicity. | Drug | Phase 1 Dose Escalation of PX-866 + vemurafenib, Phase 2 Combination PX-866 + vemurafenib |
| vemurafenibAlso: Zelborafvemurafenib is a B-Raf enzyme inhibitor | Drug | Phase 1 Dose Escalation of PX-866 + vemurafenib, Phase 2 Combination PX-866 + vemurafenib, Phase 2 Single-agent vemurafenib |
Primary outcome
Incidence and severity of adverse events (phase 1)
Time frame: 28 days
Progression-free survival (PFS) (phase 2)
Time frame: 56 days
4 secondary outcomes
Plasma concentrations of PX-866 and metabolites (phase 1)
Time frame: 44 days
Objective Response Rate (ORR)(phase 2)
Time frame: 56 days
Disease Control Rate (DCR)(phase 2)
Time frame: 56 Days
Plasma concentrations of vemurafenib (phase 1)
Time frame: 44 days
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2018.
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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PX-866 and vemurafenib in people with Advanced BRAF-mutant Cancers, run by Cascadian Therapeutics Inc. at 5 sites in United States.
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 14 inclusion and 11 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: stopped early, as of the sponsor's last update on 16 May 2018. 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 United States. 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 was stopped early (reason given: slow accrual). Results are not available in the source record.
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?
Incidence and severity of adverse events (phase 1) (time frame: 28 days). The study lists 2 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 16 May 2018; AzTrials last refreshed its copy on 7 Nov 2026.