Metastatic Breast CancerPhase 1/2NCT00924352
Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer
A Phase 1/2 study testing Dasatinib and Ixabepilone in people with Metastatic Breast Cancer, run by Accelerated Community Oncology Research Network at 13 sites in United States.
Trial summary
The primary objective for the Phase I portion of the study is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) and for the Phase II portion of the study is to evaluate progression free survival (PFS). Secondary objectives are response rate, clinical benefit rate, and overall toxicity. 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?
- Dasatinib and Ixabepilone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 13 sitesUnited States
- Study dates
- Jun 2009to Oct 2013
- 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
- A patient must meet each of the following criteria to be considered eligible for inclusion in this study:
- Patient has the ability to understand and the willingness to sign a written informed consent including form according to institutional guidelines.
- Patient has histologically-proven breast cancer.
- Patient has locally recurrent or metastatic disease, measurable or non- measurable by RECIST criteria.
- Patient has HER2-negative disease or disease that is refractory to HER2- directed therapy.
- Patient is female or male ≥ 18 years of age.
Show all 24Show fewer
- Patient has(ECOG)performance status of ≤ 2.
- Patient must have received at least 1 but no more than 2 prior chemotherapy regimens for locally recurrent or metastatic disease. Patients may have received neoadjuvant and/or adjuvant chemotherapy. These prior regimens can not have included ixabepilone or dasatinib. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
- Prior chemotherapy must have been completed at least 3 weeks prior to study treatment start (6 weeks for nitrosoureas and mitomycin), and the patient must have recovered from all associated toxicities (except for alopecia and neuropathy grade 1 according to CTCAE, v3.0 classification).
- Radiation therapy, immunotherapy, biologic therapy, and hormonal/endocrine therapy must have been completed at least 2 weeks prior to study treatment start. Any major surgery must have been completed at least 4 weeks prior to study treatment start.
- Patient has adequate organ, metabolic and bone marrow function as follows:
- Total bilirubin ≤ 1.0 × institutional ULN
- AST, ALT ≤ 2.5 × institutional ULN
- Serum sodium, potassium, calcium, magnesium, and phosphate ≥ institutional LLN. (Hypokalemia or hypomagnesemia must be corrected prior to dasatinib administration.)
- Serum creatinine < 1.5 × institutional ULN
- Hematologic function: - ANC ≥ 1500/mm3. -Platelet count ≥ 100,000/mm3. - Hemoglobin ≥ 10.0 g/dL
- PT and PTT < 1.5 x institutional ULN
- Ability to take oral medication (dasatinib must be swallowed whole).
- Concomitant medications:
- Patient agrees to discontinue St John's Wort at least 5 days prior to starting dasatinib therapy and while receiving dasatinib therapy.
- Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
- The use of CYP3A4 inducers, inhibitors, and substrates; medications that prolong QT interval; antacids; H2 blockers and proton pump inhibitors; and medications that inhibit platelet function and anticoagulation should be avoided during dasatinib therapy. These are restricted therapies that are permitted with caution when medically indicated.
- Women of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study treatment.
- Patients of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study treatment is stopped.
Who cannot join
- A patient who meets any of the following criteria will be considered not eligible for inclusion in this study:
- Patient has had prior treatment with ixabepilone, dasatinib, or both.
- Patient has had more than 2 prior lines of chemotherapy for locally recurrent or metastatic breast cancer. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
- Patient has received a cumulative dose of > 360 mg/m2 of doxorubicin or > 600 mg/m2 of epirubicin.
- Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine).
- Patients with CTC grade 2 or greater neuropathy (motor or sensory) at study entry.
Show all 39Show fewer
- Patient has evidence CNS or brain metastases, unless CNS or brain metastases have been treated and stable for > 3 months.
- Patient has psychiatric illness or social situation that would limit or prohibit compliance with study requirements.
- Patient has an inability to take oral medication or inability to absorb oral medication.
- Patient has had any invasive cancer other than the one being treated in this study within 3 years with the exception of surgically cured nonmelanoma skin cancer; in situ carcinoma of the cervix; in situ carcinoma of the breast.
- Patient is receiving concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for cancer).
- Patient has other serious medical conditions as judged by the Principal Investigator.
- Patient has a concurrent medical condition which may increase the risk of toxicity.
- Patient has a pleural or pericardial effusion of any grade.
- Patient has cardiac symptoms including any of the following:
- Uncontrolled angina, congestive heart failure or myocardial infarction within 6 months of study entry.
- Diagnosed congenital long QT syndrome.
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
- Prolonged QTc on pre-entry ECG (> 450 msec).
- Hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
- Patient has a history of significant bleeding disorder unrelated to cancer, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
- Ongoing or recent (≤ 3 months) significant GI bleeding.
- Patient is taking any of the following concomitant medications at study entry:
- Category I drugs that are generally accepted to have a risk of causing Torsades de pointes including (Patients must discontinue drug 7 days prior to starting dasatinib.):
- quinidine, procainamide, disopyramide.
- amiodarone, sotalol, ibutilide, dofetilide.
- erythromycin, clarithromycin.
- chlorpromazine,haloperidol,mesoridazine, thioridazine,pimozide .
- cisapride,bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,halofantrine, levomethadyl, pentamidine,sparfloxacin, lidoflazine.
- Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ixabepilone or dasatinib. Ixabepilone is contraindicated in patients who have a known, prior, severe (CTC grade 3 or 4) history of hypersensitivity reaction to a drug formulated in Cremophor® EL (polyoxyethylated castor oil).
- Patient has received any investigational agent or therapy within 30 days prior to study treatment start.
- Patient is unwilling or unable to comply with study requirements.
- Women who:
- are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study treatment, or
- have a positive pregnancy test at baseline, or
- are pregnant or breastfeeding.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, 52722
Hematology Oncology Centers of the Northern Rockies
Billings, Montana, 59101
Oncology Hematology Specialists, P.A.
Denville, New Jersey, 07834
The Moses H. Cone Regional Cancer Center
Greensboro, North Carolina, 27403
Central Georgia Cancer Care
Macon, Georgia, 31201
Northwest Georgia Oncology Centers
Marietta, Georgia, 30060
University of Tennessee Cancer Institute
Memphis, Tennessee, 38104
The West Clinic
Memphis, Tennessee, 38120
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, 19106
North Coast Cancer Care
Sandusky, Ohio, 44870
North Shore Cancer Research
Skokie, Illinois, 60076
Baystate Medical Center
Springfield, Massachusetts, 01107
Hematology Oncology PC
Stamford, Connecticut, 06902
About this study
Official title: Phase I/II Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer
The primary objective for the Phase I portion of the study is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) and for the Phase II portion of the study is to evaluate progression free survival (PFS). Secondary objectives are response rate, clinical benefit rate, and overall toxicity.
Read the detailed description
In the Phase I portion of the study, patients will receive study treatment according to the assigned dose level. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Dasatinib will be administered continuously starting on Day 1, Cycle 1 once daily (QD).
Three patients will be enrolled at dose level 0 and observed for dose-limiting toxicity (DLT) for 1 course of treatment.
Dose escalation or reduction will depend on the number of patients experiencing DLT as follows:
- If 0 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at the next higher dose level.
- If 1 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at that dose level.
- If 2 of 3 or 3 of 3 patients experience a DLT, then 3 patients will be enrolled at the next lower dose unless 6 patients have already been treated at that dose.
- If ≥2 of 6 patients experience a DLT at that dose level, then the MTD is considered to have been exceeded. At that point, 3 patients are treated at the next lower dose.
- If no more than 1 of the 6 patients experiences a DLT, then the dose level will be escalated 1 level.
Maximum-tolerated dose (MTD) is defined as the dose at which ≤1 of 6 patients experience DLT, and above which ≥2 of 6 patients experience DLT.
In the Phase II portion of the study, dasatinib and ixabepilone will be administered at the MTD determined during Phase I. Dasatinib will be started on Day 1, Cycle 1 and will be administered continuously once daily. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Patients will be treated with both agents for up to 8 cycles, after which stable or responding patients are eligible for monotherapy with dasatinib at the investigator's discretion in the absence of disease progression or unacceptable toxicity.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Dasatinib, Ixabepilone
- Keywords
- Metastatic Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called SPRYCEL
Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD.
IxabepiloneDrug
Also called IXEMPRA
Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| Ixabepilone + Dasatinib | Experimental | Ixabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2.
Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD. Receives: Drug: Dasatinib; Drug: Ixabepilone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the Maximum Tolerated Dose (MTD) of Dasatinib When Given in Combination With Ixabepilone (Phase I)
The MTD of dasatinib (taken daily, continuously) when given in combination with ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Measured: MTD was assessed during the first cycle of combination therapy (days 1-28).
Determination of the Maximum Tolerated Dose (MTD) of Ixabepilone When Given in Combination With Dasatinib (Phase I)
The MTD of ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) when given in combination with dasatinib (taken daily, continuously) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Measured: MTD was assessed during the first cycle of combination therapy (days 1-28).
Determination of the Dose Limiting Toxicities (DLTs) of the Combination of Dasatinib and Ixabepilone (Phase I)
DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose limiting toxicity was defined as any grade 4 hematologic event or any grade 3 or 4 non-hematologic event occurring during cycle 1 that is attributable to dasatinib, ixabepilone, or the combination. The following events were excluded from this definition: grade 4 neutropenia lasting for 3 days or less; grade 3 nausea responsive to antiemetics; grade 3 infection with normal ANC or grade 1 or 2 neutrophils; grade 3 diarrhea responsive to optimal use of antidiarrheal therapy.
Measured: DLTs were assessed during the first cycle of combination therapy (days 1-28).
Evaluation of Progression-free Survival (PFS) of the Combination of Dasatinib and Ixabepilone (Phase II)
Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Measured: PFS was measured from day 1 of treatment until time of progression (assessed about every 8 weeks) or death, whichever came first, for up to 27.2 months.
Secondary outcomes (4)
Best Overall Response of the Combination of Dasatinib and Ixabepilone (Phase II)
Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Measured: Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.
Clinical Benefit Rate of the Combination of Dasatinib and Ixabepilone (Phase II)
Clinical benefit rate was defined as the percentage of participants experiencing stable disease (SD) of at least 24 weeks (from the start of treatment) plus complete response (CR) and partial response (PR). Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where CR is the disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter(LD) of target lesions; SD is neither sufficient shrinkage in sum of longest diameter of target lesions to be PR nor increase of >=20%.
Measured: Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.
Incidence of Grade 3 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)
All treatment emergent adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.
Incidence of Grade 4 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)
All treatment emergent adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionOct 2013
- Study completionOct 2013
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Accelerated Community Oncology Research Network
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Lee S. Schwartzberg, MD, FACP, Study chair, The West Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00924352
- Sponsor's protocol ID
- ALSSMBC0804
- Status last verified
- Oct 2014
- First submitted
- 16 Jun 2009
- Last updated
- 13 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Dasatinib Plus Ixabepilone in 2nd or 3rd Line Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00924352
- Acronym / sponsor ID
- ALSSMBC0804
- Conditions
- Metastatic Breast Cancer
- Keywords
- Metastatic Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Accelerated Community Oncology Research NetworkUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2009
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 29 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective for the Phase I portion of the study is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) and for the Phase II portion of the study is to evaluate progression free survival (PFS). Secondary objectives are response rate, clinical benefit rate, and overall toxicity.
Detailed description
In the Phase I portion of the study, patients will receive study treatment according to the assigned dose level. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Dasatinib will be administered continuously starting on Day 1, Cycle 1 once daily (QD).
Three patients will be enrolled at dose level 0 and observed for dose-limiting toxicity (DLT) for 1 course of treatment.
Dose escalation or reduction will depend on the number of patients experiencing DLT as follows:
- If 0 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at the next higher dose level.
- If 1 of 3 patients experiences a DLT, then 3 additional patients will be enrolled at that dose level.
- If 2 of 3 or 3 of 3 patients experience a DLT, then 3 patients will be enrolled at the next lower dose unless 6 patients have already been treated at that dose.
- If ≥2 of 6 patients experience a DLT at that dose level, then the MTD is considered to have been exceeded. At that point, 3 patients are treated at the next lower dose.
- If no more than 1 of the 6 patients experiences a DLT, then the dose level will be escalated 1 level.
Maximum-tolerated dose (MTD) is defined as the dose at which ≤1 of 6 patients experience DLT, and above which ≥2 of 6 patients experience DLT.
In the Phase II portion of the study, dasatinib and ixabepilone will be administered at the MTD determined during Phase I. Dasatinib will be started on Day 1, Cycle 1 and will be administered continuously once daily. Ixabepilone will be administered over 1 hour on Days 1, 8, and 15 of a 28-day cycle. Patients will be treated with both agents for up to 8 cycles, after which stable or responding patients are eligible for monotherapy with dasatinib at the investigator's discretion in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ixabepilone + Dasatinib | Experimental | Drug: Dasatinib, Drug: IxabepiloneIxabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2. Dasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- A patient must meet each of the following criteria to be considered eligible for inclusion in this study:
- Patient has the ability to understand and the willingness to sign a written informed consent including form according to institutional guidelines.
- Patient has histologically-proven breast cancer.
- Patient has locally recurrent or metastatic disease, measurable or non- measurable by RECIST criteria.
- Patient has HER2-negative disease or disease that is refractory to HER2- directed therapy.
Key exclusion criteria (39 listed)
- A patient who meets any of the following criteria will be considered not eligible for inclusion in this study:
- Patient has had prior treatment with ixabepilone, dasatinib, or both.
- Patient has had more than 2 prior lines of chemotherapy for locally recurrent or metastatic breast cancer. A line of chemotherapy will be defined as one or more agents used continuously or discontinuously (i.e., allowing a break or chemo holiday) without the addition of a new agent. Hormonal therapy will not be considered a line of therapy.
- Patient has received a cumulative dose of > 360 mg/m2 of doxorubicin or > 600 mg/m2 of epirubicin.
- Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine).
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 |
|---|---|---|
| DasatinibAlso: SPRYCELDasatinib tablets will be administered continuously starting on Day 1, Cycle 1 once daily (QD).Dose Level 2;140 mg QD,Dose Level 1;100 mg QD,Dose Level 0 (Starting Dose);100 mg QD,Dose Level - 1;100 mg QD,Dose Level - 2;70 mg QD. | Drug | Ixabepilone + Dasatinib |
| IxabepiloneAlso: IXEMPRAIxabepilone, for injection 15 mg supplied with diluent for ixabepilone, 8 mL. Dose Level 2;20 mg/m2,Dose Level 1;20 mg/m2,Dose Level 0 (Starting Dose);16 mg/m2,Dose Level - 1;12 mg/m2,Dose Level - 2;12 mg/m2. | Drug | Ixabepilone + Dasatinib |
Primary outcome
Determination of the Maximum Tolerated Dose (MTD) of Dasatinib When Given in Combination With Ixabepilone (Phase I)
Time frame: MTD was assessed during the first cycle of combination therapy (days 1-28).
The MTD of dasatinib (taken daily, continuously) when given in combination with ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Determination of the Maximum Tolerated Dose (MTD) of Ixabepilone When Given in Combination With Dasatinib (Phase I)
Time frame: MTD was assessed during the first cycle of combination therapy (days 1-28).
The MTD of ixabepilone (administered on Days 1, 8, and 15 of a 28-day cycle) when given in combination with dasatinib (taken daily, continuously) was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. The MTD was defined as the dose at which ≤ 1 of 6 patients experienced DLT, and above which ≥ 2 of 6 patients experienced DLT.
Determination of the Dose Limiting Toxicities (DLTs) of the Combination of Dasatinib and Ixabepilone (Phase I)
Time frame: DLTs were assessed during the first cycle of combination therapy (days 1-28).
DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose limiting toxicity was defined as any grade 4 hematologic event or any grade 3 or 4 non-hematologic event occurring during cycle 1 that is attributable to dasatinib, ixabepilone, or the combination. The following events were excluded from this definition: grade 4 neutropenia lasting for 3 days or less; grade 3 nausea responsive to antiemetics; grade 3 infection with normal ANC or grade 1 or 2 neutrophils; grade 3 diarrhea responsive to optimal use of antidiarrheal therapy.
Evaluation of Progression-free Survival (PFS) of the Combination of Dasatinib and Ixabepilone (Phase II)
Time frame: PFS was measured from day 1 of treatment until time of progression (assessed about every 8 weeks) or death, whichever came first, for up to 27.2 months.
Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
4 secondary outcomes
Best Overall Response of the Combination of Dasatinib and Ixabepilone (Phase II)
Time frame: Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.
Clinical Benefit Rate of the Combination of Dasatinib and Ixabepilone (Phase II)
Time frame: Response to treatment was assessed after about every 8 weeks of treatment, for up to 27.2 months.
Incidence of Grade 3 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)
Time frame: Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.
Incidence of Grade 4 Adverse Events (AEs) With the Combination of Dasatinib and Ixabepilone (Phase II)
Time frame: Adverse events were collected beginning on day 1 of treatment until one month after the end of study treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
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.
Lee S. Schwartzberg, MD, FACP study chair
The West Clinic
13 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 Dasatinib and Ixabepilone in people with Metastatic Breast Cancer, run by Accelerated Community Oncology Research Network at 13 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 24 inclusion and 39 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 13 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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 29 Sep 2014). 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?
Determination of the Maximum Tolerated Dose (MTD) of Dasatinib When Given in Combination With Ixabepilone (Phase I) (time frame: MTD was assessed during the first cycle of combination therapy (days 1-28).). The study lists 4 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 13 Oct 2014.