Metastatic Breast CancerPhase 1/2NCT01596751
Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer
A Phase 1/2 study testing PLX3397 and Eribulin in people with Metastatic Breast Cancer, run by Hope Rugo, MD at 3 sites in United States.
Trial summary
The purpose of the Phase 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- PLX3397 and Eribulin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 3 sitesUnited States
- Study dates
- 12 Jul 2012to 5 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Pathologically confirmed diagnosis of breast cancer with documented progressive disease.
- Patients with stable brain metastases are eligible for this trial.
- At least one prior chemotherapy regimen for metastatic breast cancer. Prior treatment must be discontinued at least 2 weeks before treatment start.
- Concomitant therapy with bisphosphonates is allowed.
- Stable dose coumadin anticoagulation is allowed, providing that anticoagulation can be safely held to an International Normalized Ratio (INR) within normal range for the purpose of tumor biopsy. Low molecular weight heparin (LMWH is the preferred method of anticoagulation.
- Prothrombin time (PT)/International Normalized Ratio (INR) and partial thromboplastin time (PTT) within institutional normal limits within two weeks before initial biopsy.
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- Measurable disease, as defined by RECIST guidelines or evaluable disease. Bone metastases must be evaluable.
- Disease amenable to core biopsy. Patients with pulmonary metastases as their only site of disease may enroll on this trial and will not undergo biopsy.
- For Phase I: patients with human epidermal growth factor receptor 2 (HER2) overexpressing disease must have been previously treated with trastuzumab. Patients with HER2 overexpressing disease are not eligible for the Phase II trial.
- Age eighteen years or older.
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
- Life expectancy of >/= 12 weeks.
- Patients with < grade 1 peripheral neuropathy are eligible for this trial.
- Adequate bone marrow reserve: Absolute Neutrophil Count (ANC) >/= 1000, platelets >/= 100,000.
- Adequate renal function: serum creatinine </= 1.5x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 50 ml/min.
- Sodium, potassium, and chloride levels within institutional normal limits.
- Adequate hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 x ULN, and total bilirubin </= 1.5x upper limit of normal. In patients with liver dysfunction due to hepatic metastases, AST and ALT are permitted to be </= 5 times the ULN.
- At baseline: Ejection fraction (EF) ≥ 50%, no evidence of QT prolongation, no history of congenital long QT syndrome, and no use of drugs known to increase the risk of Torsades de Point - patients may be eligible for study if the drug can be changed to another agent with less risk (such as changing from citalopram to an alternate antidepressant).
- Able to take oral medications and maintain hydration.
- Ability to give written informed consent and willingness to comply with the requirements of the protocol
- Women of child-bearing potential must agree to use an effective method of birth control during treatment and for six months after receiving their last dose of study drug
- Specific inclusion criteria for Phase II
- Patients enrolling on the phase II portion of this trial must have ER, progesterone receptors (PR) and HER2 negative disease defined as less than 10% staining for ER and PR, and HER2 not amplified byFluorescent in situ hybridization (FISH), 0-1% by Immunohistochemistry (IHC), or 2+ by IHC and no evidence of amplification by FISH.
Who cannot join
- Treatment with another chemotherapy or hormonal therapy within the past 2 weeks.
- Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2 weeks.
- Concurrent treatment with radiotherapy.
- Ongoing treatment with any other investigational therapy.
- Prior treatment with eribulin
- Severe, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocol.
- Inadequate bone marrow, renal, or hepatic function as defined above, or an active coagulopathy that precludes tissue biopsy.
- Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control. Women of childbearing potential must undergo a serum pregnancy test within seven days of starting the study drug.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Duke University Cancer Center
Durham, North Carolina, 27710
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Enhancing Efficacy of Chemotherapy in Triple Negative/Basal-Like Breast Cancer by Targeting Macrophages: A Multicenter Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer
The purpose of the Phase 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer.
Read the detailed description
This is a nonrandomized, open label phase Ib/II study evaluating the safety and efficacy of eribulin in combination with PLX3397, a novel CSF1 inhibitor, in patients with metastatic breast cancer. The phase II portion of this trial will be limited to patients with triple negative disease.
The phase I portion of this trial is a dose escalation of PLX3397 to determine the maximum tolerated dose (MTD) of PLX3397 when given in combination with standard dose eribulin. Patients will be enrolled in cohorts of three, using the dose levels and plan outlined in the statistical section, with 6 patients enrolled at the MTD. All patients with accessible tumor will be required to have a tumor biopsy at study start before starting therapy. Pharmacokinetics of PLX3397 and eribulin, and blood levels of CSF1 will be obtained as outlined in section 14. To allow rapid accrual to phase Ib, and an earlier start to the phase II trial, patients will be enrolled in phase I with both hormone receptor positive and negative disease, and at any line of therapy assuming eligibility criteria are otherwise met.
Dose limiting toxicity (DLT) will be defined as any treatment-related toxicity meeting the criteria below and occurring within the first 21 days of combination therapy. Patients must receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses are due to a DLT).
Patients in each cohort will be followed for at least 3 weeks (one full cycle) before opening accrual to the next dose level. If one patient in any cohort develops a DLT, an additional 3 patients will be enrolled at that level. If no additional toxicities occur in the six patients, then this particular dose would be used for the phase II trial, and the next higher dose would be considered the MTD. A minimum of 12 and maximum of 24 patients will be enrolled in the phase I study. The phase II trial will not open until the last patient in the phase I study has been followed for at least 3 weeks.
The phase II portion of this trial will evaluate progression free survival (PFS) in patients with Triple negative breast cancer (TNBC) treated with PLX3397 and eribulin, using the dose of PLX3397 determined in the phase Ib study in a two-step design. Please see the statistical section for details regarding enrollment and statistical design. Treatment is preceded by a 5 to 7 day lead-in phase, in which patients will take PLX3397 alone daily. Patients with accessible tumor will undergo a core biopsy of tumor before the start of PLX3397 treatment, and then a fine needle aspiration or core biopsy will be performed on the day of or the day before the start of eribulin (day -1 to day 0).
- Conditions
- Metastatic Breast Cancer
- Being tested
- PLX3397, Eribulin
- Keywords
- metastatic, breast, cancer, triple, negative, PLX, Eribulin
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLX3397Drug
Dosage Form: 100 mg or 200 mg capsules, Dosage: 400 - 1000 mg, oral administration
EribulinDrug
Also called Halaven, E7389
Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib: 600 mg/Day PLX3397 Combined with Eribulin | Experimental | Treatments are given in 21 day cycles. For each cycle, treatment includes:
* PLX3397 at a dose of 600 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8. Receives: Drug: PLX3397; Drug: Eribulin |
| Phase Ib: 800 mg/Day PLX3397 Combined with Eribulin | Experimental | Treatments are given in 21 day cycles. For each cycle, treatment includes:
* PLX3397 at a dose of 800 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 Receives: Drug: PLX3397; Drug: Eribulin |
| Phase Ib: 1000 mg/Day PLX3397 Combined with Eribulin | Experimental | Treatments are given in 21 day cycles. For each cycle, treatment includes:
* PLX3397 at a dose of 1000 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 Receives: Drug: PLX3397; Drug: Eribulin |
| Phase II: 800 mg/Day PLX3397 Lead in +Combined with Eribulin | Experimental | Treatment begins with a 7 day Lead-in phase of PLX3397 alone, followed by 21 day cycles of PLX3397 in combination with eribulin.
Lead-in phase treatment:
* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest.
Treatment given in each 21 day cycle:
* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest, repeated weekly
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 Receives: Drug: PLX3397; Drug: Eribulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of PLX3397 Given in Combination With Standard Dose Eribulin in Participants With Metastatic Breast Cancer (Phase 1b)
The MTD was determined using a standard dose-escalation schema with 3 to 6 participants per cohort (3+3 design) for participants enrolled in Phase 1b. The starting dose level of PLX3397 was 600 mg/day and was raised in successive cohorts up to a dose of 1000 mg/day. Participants in each Phase Ib cohort were followed for dose limiting toxicities (DLTs) within the first 21 days of combination therapy and had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A toxicity was considered a DLT if it was treatment related and met specific requirements for type of toxicity and severity assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4. The MTD was defined as the lowest dose level at which 2 or more participants in a cohort experienced a DLT. The dose level just below the MTD was selected for Phase 2.
Measured: Up to Day 21
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (Phase Ib)
DLTs are select treatment related toxicities described in the protocol that were Grade 3 or 4 in severity per CTCAE v4, occurring within the first 21 days of combination therapy for patients enrolled in Phase Ib (for example, Grade 3 thrombocytopenia with significant bleeding, Grade 4 neutropenia lasting more than 5 days, or any Grade 3 or higher non-hematologic toxicity other than alopecia unless clearly unrelated to treatment). Grade 3 and 4 toxicities are considered severe and may be life threatening. Participants had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A treatment delay of greater than 7 days for PLX3397 or inability to get two doses of eribulin in the first cycle due to toxicity that was unrelated to cancer worsening or other illness was considered a DLT.
Measured: Up to Day 21
Percentage of Total Phase II Participants With Chemotherapy Pre-Treated Triple Negative Metastatic Breast Cancer Who Are Progression Free at 3 Months
Progression-free survival (PFS) at 3 months is defined as the proportion of participants in the combined Phase II cohorts that are alive and progression-free 90 days after Study Day 1, from the first administration of PLX3397 with eribulin. Duration of PFS is defined as the time from Study Day 1 to the earlier of disease progression or death due to any cause. These analyses are designed to include only objective progression events per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PFS will be estimated as a simple percentage based upon the results of the 3 month tumor assessment. Participants for whom this assessment is not performed will be included as failures, even if known to be alive at this time point. Confidence intervals will be provided.
Measured: Up to 3 months
Secondary outcomes (3)
Objective Response Rate (ORR) (Phase II)
The objective response rate (ORR) is defined as the proportion of patients for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or confirmed partial response (PR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 criteria. The analysis of ORR employed the Per Protocol population. Patients who did not have any post-baseline tumor assessments were counted as non-responders.
Measured: From baseline until study completion, an average of 24 months
Median Duration of Response (Phase II)
Duration of response is defined as the time from first documentation of objective response that is subsequently confirmed to progressive disease (PD) by the criteria or death due to any cause. Responders who have not been documented to have progressed or died at time of data cutoff will be right censored at the last available adequate tumor assessment. Median duration of response and its associated confidence interval will be estimated using the Kaplan-Meier method.
Measured: From date of first confirmed disease response to confirmed disease progression or death due to any cause, an average of 2 months
Median Time to Disease Progression (Phase II)
Time to progression will be estimated using the Kaplan-Meier method. Efficacy responses, disease progression and relapse classified based on RECIST v1.1 criteria will be used to determine progression. Time to progression will be calculated from the first administration of PLX3397 with eribulin. Participants who do not have disease progression will be censored at the date of the last evaluation for study disease or at the time of initiation of the new therapy, whichever is earlier. Patients lacking any response assessment after randomization will be censored at Day 1
Measured: From Day 1 to date of disease progression, an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2012 (estimated)
- Study start12 Jul 2012
- Primary completion5 Jul 2017
- Study completion5 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hope Rugo, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation, Plexxikon
- Responsible party
- Sponsor-investigator, Hope Rugo, MD, University of California, San Francisco
- Investigators
- Hope S. Rugo, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01596751
- Sponsor's protocol ID
- 12751
- Other IDs
- NCI-2015-01321
- Status last verified
- Jul 2020
- First submitted
- 7 May 2012
- Last updated
- 17 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Efficacy of Chemotherapy in Triple Negative/Basal-Like Breast Cancer by Targeting Macrophages: A Multicenter Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01596751
- Acronym / sponsor ID
- 12751
- Conditions
- Metastatic Breast Cancer
- Keywords
- metastatic, breast, cancer, triple, negative, PLX, Eribulin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Hope Rugo, MDUniversity, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation, Plexxikon
- Study start
- 12 Jul 2012 (actual)
- Primary completion
- 5 Jul 2017 (actual)
- Study completion
- 5 Jul 2019 (actual)
- First posted
- 11 May 2012 (estimated)
- Results
- Posted 14 May 2020
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 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer.
Detailed description
This is a nonrandomized, open label phase Ib/II study evaluating the safety and efficacy of eribulin in combination with PLX3397, a novel CSF1 inhibitor, in patients with metastatic breast cancer. The phase II portion of this trial will be limited to patients with triple negative disease.
The phase I portion of this trial is a dose escalation of PLX3397 to determine the maximum tolerated dose (MTD) of PLX3397 when given in combination with standard dose eribulin. Patients will be enrolled in cohorts of three, using the dose levels and plan outlined in the statistical section, with 6 patients enrolled at the MTD. All patients with accessible tumor will be required to have a tumor biopsy at study start before starting therapy. Pharmacokinetics of PLX3397 and eribulin, and blood levels of CSF1 will be obtained as outlined in section 14. To allow rapid accrual to phase Ib, and an earlier start to the phase II trial, patients will be enrolled in phase I with both hormone receptor positive and negative disease, and at any line of therapy assuming eligibility criteria are otherwise met.
Dose limiting toxicity (DLT) will be defined as any treatment-related toxicity meeting the criteria below and occurring within the first 21 days of combination therapy. Patients must receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses are due to a DLT).
Patients in each cohort will be followed for at least 3 weeks (one full cycle) before opening accrual to the next dose level. If one patient in any cohort develops a DLT, an additional 3 patients will be enrolled at that level. If no additional toxicities occur in the six patients, then this particular dose would be used for the phase II trial, and the next higher dose would be considered the MTD. A minimum of 12 and maximum of 24 patients will be enrolled in the phase I study. The phase II trial will not open until the last patient in the phase I study has been followed for at least 3 weeks.
The phase II portion of this trial will evaluate progression free survival (PFS) in patients with Triple negative breast cancer (TNBC) treated with PLX3397 and eribulin, using the dose of PLX3397 determined in the phase Ib study in a two-step design. Please see the statistical section for details regarding enrollment and statistical design. Treatment is preceded by a 5 to 7 day lead-in phase, in which patients will take PLX3397 alone daily. Patients with accessible tumor will undergo a core biopsy of tumor before the start of PLX3397 treatment, and then a fine needle aspiration or core biopsy will be performed on the day of or the day before the start of eribulin (day -1 to day 0).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase Ib: 600 mg/Day PLX3397 Combined with Eribulin | Experimental | Drug: PLX3397, Drug: EribulinTreatments are given in 21 day cycles. For each cycle, treatment includes: * PLX3397 at a dose of 600 mg/day taken by mouth in the form of 100-200 mg gelcaps * Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8. |
| Phase Ib: 800 mg/Day PLX3397 Combined with Eribulin | Experimental | Drug: PLX3397, Drug: EribulinTreatments are given in 21 day cycles. For each cycle, treatment includes: * PLX3397 at a dose of 800 mg/day taken by mouth in the form of 100-200 mg gelcaps * Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 |
| Phase Ib: 1000 mg/Day PLX3397 Combined with Eribulin | Experimental | Drug: PLX3397, Drug: EribulinTreatments are given in 21 day cycles. For each cycle, treatment includes: * PLX3397 at a dose of 1000 mg/day taken by mouth in the form of 100-200 mg gelcaps * Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 |
| Phase II: 800 mg/Day PLX3397 Lead in +Combined with Eribulin | Experimental | Drug: PLX3397, Drug: EribulinTreatment begins with a 7 day Lead-in phase of PLX3397 alone, followed by 21 day cycles of PLX3397 in combination with eribulin. Lead-in phase treatment: * PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest. Treatment given in each 21 day cycle: * PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest, repeated weekly * Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Pathologically confirmed diagnosis of breast cancer with documented progressive disease.
- Patients with stable brain metastases are eligible for this trial.
- At least one prior chemotherapy regimen for metastatic breast cancer. Prior treatment must be discontinued at least 2 weeks before treatment start.
- Concomitant therapy with bisphosphonates is allowed.
- Stable dose coumadin anticoagulation is allowed, providing that anticoagulation can be safely held to an International Normalized Ratio (INR) within normal range for the purpose of tumor biopsy. Low molecular weight heparin (LMWH is the preferred method of anticoagulation.
Key exclusion criteria (8 listed)
- Treatment with another chemotherapy or hormonal therapy within the past 2 weeks.
- Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2 weeks.
- Concurrent treatment with radiotherapy.
- Ongoing treatment with any other investigational therapy.
- Prior treatment with eribulin
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 |
|---|---|---|
| PLX3397Dosage Form: 100 mg or 200 mg capsules, Dosage: 400 - 1000 mg, oral administration | Drug | Phase II: 800 mg/Day PLX3397 Lead in +Combined with Eribulin, Phase Ib: 1000 mg/Day PLX3397 Combined with Eribulin, Phase Ib: 600 mg/Day PLX3397 Combined with Eribulin, Phase Ib: 800 mg/Day PLX3397 Combined with Eribulin |
| EribulinAlso: Halaven, E7389Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days | Drug | Phase II: 800 mg/Day PLX3397 Lead in +Combined with Eribulin, Phase Ib: 1000 mg/Day PLX3397 Combined with Eribulin, Phase Ib: 600 mg/Day PLX3397 Combined with Eribulin, Phase Ib: 800 mg/Day PLX3397 Combined with Eribulin |
Primary outcome
Maximum Tolerated Dose (MTD) of PLX3397 Given in Combination With Standard Dose Eribulin in Participants With Metastatic Breast Cancer (Phase 1b)
Time frame: Up to Day 21
The MTD was determined using a standard dose-escalation schema with 3 to 6 participants per cohort (3+3 design) for participants enrolled in Phase 1b. The starting dose level of PLX3397 was 600 mg/day and was raised in successive cohorts up to a dose of 1000 mg/day. Participants in each Phase Ib cohort were followed for dose limiting toxicities (DLTs) within the first 21 days of combination therapy and had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A toxicity was considered a DLT if it was treatment related and met specific requirements for type of toxicity and severity assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4. The MTD was defined as the lowest dose level at which 2 or more participants in a cohort experienced a DLT. The dose level just below the MTD was selected for Phase 2.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (Phase Ib)
Time frame: Up to Day 21
DLTs are select treatment related toxicities described in the protocol that were Grade 3 or 4 in severity per CTCAE v4, occurring within the first 21 days of combination therapy for patients enrolled in Phase Ib (for example, Grade 3 thrombocytopenia with significant bleeding, Grade 4 neutropenia lasting more than 5 days, or any Grade 3 or higher non-hematologic toxicity other than alopecia unless clearly unrelated to treatment). Grade 3 and 4 toxicities are considered severe and may be life threatening. Participants had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A treatment delay of greater than 7 days for PLX3397 or inability to get two doses of eribulin in the first cycle due to toxicity that was unrelated to cancer worsening or other illness was considered a DLT.
Percentage of Total Phase II Participants With Chemotherapy Pre-Treated Triple Negative Metastatic Breast Cancer Who Are Progression Free at 3 Months
Time frame: Up to 3 months
Progression-free survival (PFS) at 3 months is defined as the proportion of participants in the combined Phase II cohorts that are alive and progression-free 90 days after Study Day 1, from the first administration of PLX3397 with eribulin. Duration of PFS is defined as the time from Study Day 1 to the earlier of disease progression or death due to any cause. These analyses are designed to include only objective progression events per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PFS will be estimated as a simple percentage based upon the results of the 3 month tumor assessment. Participants for whom this assessment is not performed will be included as failures, even if known to be alive at this time point. Confidence intervals will be provided.
3 secondary outcomes
Objective Response Rate (ORR) (Phase II)
Time frame: From baseline until study completion, an average of 24 months
Median Duration of Response (Phase II)
Time frame: From date of first confirmed disease response to confirmed disease progression or death due to any cause, an average of 2 months
Median Time to Disease Progression (Phase II)
Time frame: From Day 1 to date of disease progression, an average of 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Hope S. Rugo, MD principal investigator
University of California, San Francisco
3 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 PLX3397 and Eribulin in people with Metastatic Breast Cancer, run by Hope Rugo, MD at 3 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 23 inclusion and 8 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 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
Yes. Results are posted in the registry (first posted 14 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (MTD) of PLX3397 Given in Combination With Standard Dose Eribulin in Participants With Metastatic Breast Cancer (Phase 1b) (time frame: Up to Day 21). The study lists 3 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 17 Jul 2020.