Breast CancerPhase 1/2NCT00820170
Dasatinib In Combination With Weekly Paclitaxel For Patients With Metastatic Breast Carcinoma CA 180 194
A Phase 1/2 study testing Dasatinib and Paclitaxel in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to find the highest dose of dasatinib that can be safely given to a patient when the drug is given in combination with the known anticancer drug paclitaxel. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Dasatinib and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Aug 2018
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male patients with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC.
- For the phase I portion, patients with any ER/PR/HER2 disease status, no longer eligible for hormonal therapy or HER2-targeted therapy, will be eligible.
- For the phase II portion, there needs to be documentation of negative HER2 (IHC 0-1+ or FISH/CISH negative) status. Patients with any ER/PR disease status are eligible.
- A paraffin-embedded tissue block or unstained slides from prior surgery must be available.
- Evidence of recurrent or progressive locally advanced or metastatic breast cancer.
- Presence of:
Show all 42Show fewer
- For the phase I portion: at least one evaluable or measurable metastatic lesion ,
- For the phase II portion: at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: > or = to 10 mm measured by spiral CT or > or = to 20 mm measured by conventional techniques.
- Prior therapies:
- For the phase I portion: Any number of prior endocrine or biologic therapies is permitted . In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens.
- For the phase II portion: 0-2 prior therapies for metastatic disease are allowed.
- Prior taxane therapy, either in the adjuvant or in the metastatic setting, either deliver weekly, q 2 weeks or q 3 weeks, will be permitted. Prior therapy with bevacizumab will be allowed. All previous chemotherapy, radiotherapy and intravenous biphosphonates must have been discontinued at least 3 weeks prior to study entry, 3 weeks also for trastuzumab and bevacizumab. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTC (Version 3) Grade ≤1.
- Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted, however it must be discontinued before enrolling in the study.
- ECOG performance status of 0 or 1.
- Age > or = to 18 years old. Adequate Organ Function
- Total bilirubin ≤ 1.5 times the institutional Upper Limit of Normal (ULN)
- Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN
- Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN)
- Serum Creatinine ≤ 1.5 time the institutional ULN
- Neutrophil count, Platelets, both Grade 0-1
- PT (INR) and PTT Grade 0-1, except for patients on Coumadin or low molecular weight heparin
- Ability to take oral medication (dasatinib must be swallowed whole)
- Concomitant Medications:
- Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy
- Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia. Concomitant Medications, any of the following should be considered for exclusion:
- Patient agrees to discontinue QT-prolonging agents strongly associated with Torsades de Pointes including: (patients must discontinue drug ≥ 7 days prior to starting dasatinib) such as:
- 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.
- The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.
- Patient may not be receiving any potent CYP3A4 inhibitors. These are prohibited (patients must discontinue drug ≥7 days prior to starting dasatinib) and include:
- itraconazole, ketoconazole, miconazole, coriconazole
- amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir
- ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid
- ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin
- Women of childbearing potential (WOCBP) must have:
- A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
- Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
- Pregnant or nursing women may not participate. Patients of reproductive potential may not participate unless they have agreed to use an effective method of contraception and to continue contraception for 30 days from the date of the last study drug administration. Postmenopausal woman must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Signed written informed consent including a HIPAA form according to institutional guidelines.
Who cannot join
- Life expectancy < 3 months.
- Prior severe allergic reaction to paclitaxel therapy.
- Presence of new or recurrent pleural effusion which is symptomatic and/or requiring medical intervention (NCI CTC Grade 2, 3 or 4).
- Completion of previous chemotherapy regimen < 3 weeks prior to the start of study treatment.
- Prior hormonal therapy must be discontinued prior to treatment start. Biologic therapy (eg, bevacizumab, trastuzumab) for the treatment of metastatic disease must be discontinued > or = to 3 weeks from the start of protocol treatment.
- Concurrent medical condition which may increase the risk of toxicity.
Show all 23Show fewer
- Patients may not have any clinically significant cardiovascular disease including the following:
- myocardial infarction or ventricular tachyarrhythmia within 6 months
- prolonged QTc >480 msec (Fridericia correction)
- ejection fraction less than institutional normal
- major conduction abnormality (unless a cardiac pacemaker is present)
- Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study.
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
- 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 antifactor VIII antibodies)
- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding Other medical condition which in the opinion of the Investigator might confer an unacceptable increase in risk.
- Patients with symptomatic CNS metastases that remain untreated by radiation therapy are excluded from this trial. The presence of asymptomatic brain metastases or brain metastases that have been previously irradiated are not grounds for trial exclusion.
- History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
- Presence of uncontrolled gastrointestinal malabsorption syndrome.
- Unwillingness to give written informed consent or unwillingness to participate or inability to comply with the protocol for the duration of the study. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures are necessary for participation in this clinical trial.
- Concurrent radiotherapy is not permitted for disease progression on treatment on protocol, but might allowed for pre-existing non-target lesions with approval from the principal investigator of the trial.
- Patients with > Grade 1 neuropathy will be excluded form this trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase I-II Study of Dasatinib in Combination With Weekly Paclitaxel for Patients With Metastatic Breast Carcinoma
The purpose of this study is to find the highest dose of dasatinib that can be safely given to a patient when the drug is given in combination with the known anticancer drug paclitaxel. Paclitaxel is an established anti-cancer drug, used in the treatment of many cancers, and it is an approved treatment for breast cancer. Dasatinib has been approved by the Food and Drug Administration for use as a single therapy in another kind of cancer, but its use in breast cancer patients, and in combination with paclitaxel is investigational.
In this study, we will test the safety of dasatinib when given at different dose levels in combination with paclitaxel. We want to find out what effects, good and/or bad, it has on the patient and on metastatic breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Dasatinib and Paclitaxel
- Keywords
- Breast, Cancer, DASATINIB, TAXOL (PACLITAXEL), 08-122
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dasatinib and PaclitaxelDrug
A treatment cycle will consist of 28 days, according to the following schedule:
Dasatinib 120MG PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.
The trial will initially test the combination of weekly paclitaxel and dasatinib given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort (0), the next cohort will test dasatinib given with a different schedule, 5 days on and 2 days off, omitting dasatinib the day prior and the day of administration of paclitaxel.
| Study group | Role | What they receive |
|---|---|---|
| dasatinib and paclitaxel | Experimental | The phase I portion is a standard, three-patient per cohort, dose escalation schedule will be used. Between 6 and 54 patients will likely be necessary to determine the MTD of dasatinib in combination with weekly paclitaxel.
The phase II portion of this trial has a Simon two-stage design to determine the efficacy of dasatinib when administered in combination with paclitaxel. Receives: Drug: Dasatinib and Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel.
Measured: Through completion of Phase I, up to 1 year
Efficacy (Objective Response Rate; ORR; Complete Response (CR) + Partial Response (PR)) of Dasatinib When Administered in Combination With Weekly Paclitaxel at the MTD Established During the Phase I Portion of This Trial.
Measured: Through study completion, up to 2 years
Secondary outcomes (7)
Median Overall Survival for Phase II Participants
Overall Survival for Phase II Participants
Measured: Through study completion, up to 2 years
Participant Adverse Events to Measure Safety and Tolerability of Dasatinib When Administered in Combination With Weekly Paclitaxel.
Evaluate adverse events using CTCAE v3
Measured: Through study completion, up to 2 years
Median Progression Free Survival for Phase II Participants
Per RECIST criteria, Progression (PD) is defined at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Through study completion, up to 2 years
Phase II: Number of Participants With Clinical Benefit According to Tumor Biomarker Data: Assays of VEGFR2
Tumor biomarker data obtained at baseline and after 2 cycles of treatment (8 weeks), will be performed by enzyme-linked immunosorbent assay. Clinical Benefit is defined as the sum of the percentage of participants who achieved CR, PR and stable disease for > 6 months.
Measured: 8 weeks
Median Time To Progression for Phase II Participants
Measured: Through study completion, up to 2 years
Phase II: Number of Participants With Clinical Benefit According to Circulating Tumor Cells (CTC) at Baseline and After 2 Cycles of Treatment (8 Weeks)
Phase II participants only
Measured: 8 weeks
Phase II: Exploratory Somatic Gene Mutations Detection in Archived Tumor Samples
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionAug 2018
- Study completionAug 2018
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 Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Monica Fornier, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00820170
- Sponsor's protocol ID
- 08-122
- Status last verified
- Aug 2018
- First submitted
- 8 Jan 2009
- Last updated
- 13 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study of Dasatinib in Combination With Weekly Paclitaxel for Patients With Metastatic Breast Carcinoma
- ClinicalTrials.gov ID
- NCT00820170
- Acronym / sponsor ID
- 08-122
- Conditions
- Breast Cancer
- Keywords
- Breast, Cancer, DASATINIB, TAXOL (PACLITAXEL), 08-122
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jan 2009
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 12 Jan 2009 (estimated)
- Results
- Posted 13 Aug 2019
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 find the highest dose of dasatinib that can be safely given to a patient when the drug is given in combination with the known anticancer drug paclitaxel. Paclitaxel is an established anti-cancer drug, used in the treatment of many cancers, and it is an approved treatment for breast cancer. Dasatinib has been approved by the Food and Drug Administration for use as a single therapy in another kind of cancer, but its use in breast cancer patients, and in combination with paclitaxel is investigational.
In this study, we will test the safety of dasatinib when given at different dose levels in combination with paclitaxel. We want to find out what effects, good and/or bad, it has on the patient and on metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dasatinib and paclitaxel | Experimental | Drug: Dasatinib and PaclitaxelThe phase I portion is a standard, three-patient per cohort, dose escalation schedule will be used. Between 6 and 54 patients will likely be necessary to determine the MTD of dasatinib in combination with weekly paclitaxel. The phase II portion of this trial has a Simon two-stage design to determine the efficacy of dasatinib when administered in combination with paclitaxel. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Female or male patients with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC.
- For the phase I portion, patients with any ER/PR/HER2 disease status, no longer eligible for hormonal therapy or HER2-targeted therapy, will be eligible.
- For the phase II portion, there needs to be documentation of negative HER2 (IHC 0-1+ or FISH/CISH negative) status. Patients with any ER/PR disease status are eligible.
- A paraffin-embedded tissue block or unstained slides from prior surgery must be available.
- Evidence of recurrent or progressive locally advanced or metastatic breast cancer.
Key exclusion criteria (23 listed)
- Life expectancy < 3 months.
- Prior severe allergic reaction to paclitaxel therapy.
- Presence of new or recurrent pleural effusion which is symptomatic and/or requiring medical intervention (NCI CTC Grade 2, 3 or 4).
- Completion of previous chemotherapy regimen < 3 weeks prior to the start of study treatment.
- Prior hormonal therapy must be discontinued prior to treatment start. Biologic therapy (eg, bevacizumab, trastuzumab) for the treatment of metastatic disease must be discontinued > or = to 3 weeks from the start of protocol treatment.
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 |
|---|---|---|
| Dasatinib and PaclitaxelA treatment cycle will consist of 28 days, according to the following schedule: Dasatinib 120MG PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle. The trial will initially test the combination of weekly paclitaxel and dasatinib given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort (0), the next cohort will test dasatinib given with a different schedule, 5 days on and 2 days off, omitting dasatinib the day prior and the day of administration of paclitaxel. | Drug | dasatinib and paclitaxel |
Primary outcome
Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel.
Time frame: Through completion of Phase I, up to 1 year
Efficacy (Objective Response Rate; ORR; Complete Response (CR) + Partial Response (PR)) of Dasatinib When Administered in Combination With Weekly Paclitaxel at the MTD Established During the Phase I Portion of This Trial.
Time frame: Through study completion, up to 2 years
7 secondary outcomes
Median Overall Survival for Phase II Participants
Time frame: Through study completion, up to 2 years
Participant Adverse Events to Measure Safety and Tolerability of Dasatinib When Administered in Combination With Weekly Paclitaxel.
Time frame: Through study completion, up to 2 years
Median Progression Free Survival for Phase II Participants
Time frame: Through study completion, up to 2 years
Phase II: Number of Participants With Clinical Benefit According to Tumor Biomarker Data: Assays of VEGFR2
Time frame: 8 weeks
Median Time To Progression for Phase II Participants
Time frame: Through study completion, up to 2 years
Phase II: Number of Participants With Clinical Benefit According to Circulating Tumor Cells (CTC) at Baseline and After 2 Cycles of Treatment (8 Weeks)
Time frame: 8 weeks
Phase II: Exploratory Somatic Gene Mutations Detection in Archived Tumor Samples
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Monica Fornier, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site 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 Paclitaxel in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site 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 42 inclusion and 23 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 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 13 Aug 2019). 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?
Phase I Portion: Maximum Tolerated Dose/MTD of Dasatinib When Administered in Combination With a Fixed Dose of Weekly Paclitaxel. (time frame: Through completion of Phase I, up to 1 year). 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 13 Aug 2019.