Breast CancerPhase 2NCT01332630
TPI 287 in Breast Cancer Metastatic to the Brain
A Phase 2 study testing TPI 287, Dexamethasone and Benadryl in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of the first part of this clinical research study is to find the highest tolerable dose of TPI-287 in patients with breast cancer that has spread to the brain. The goal of the second part of this study is to learn if TPI-287 can control breast cancer that has spread to the brain. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- TPI 287, Dexamethasone and Benadryl
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2011to 14 Apr 2017
- Phase
- Phase 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically proven breast cancer with metastatic disease to the brain.
- Patients must have measurable disease on MRI that has progressed after prior therapy. PD will be defined as a>/= 25% increase in the sum of the products of greatest perpendicular diameters of all measurable disease over the smallest sum observed (since treatment started) on Gd-MRI, the appearance of new lesions on scan, or clinical or neurologic worsening despite stable disease on the last 2 scans.
- Patients may have had any number of prior surgeries, radiation and/or chemotherapy regimens as adjuvant, neoadjuvant or palliative therapy for the treatment of their disease
- Patients must be >/=18 years of age.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
- Patients must have adequate bone marrow function as evidenced by an absolute neutrophil count >/=1,500/microliters and a platelet count >/=100,000/microliter, adequate renal function as evidenced by serum creatinine </=2.0 mg/dL, adequate hepatic function as evidenced by serum total bilirubin </=2.0 mg/dL, AST/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) </= 3X the upper limit of normal (ULN).
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- Patients must have recovered and healed from the effects of any prior surgery, must have received prior chemotherapy at least 2 weeks prior to dosing with adequate recovery of white blood cell count (WBC) and platelet counts, and at least 12 weeks must have elapsed from the completion of radiotherapy, unless there are new lesions appearing on imaging within this 12 weeks frame.
- Women of child-bearing potential (i.e. </= 50 years of age or has had menstrual cycle within the past 12 months, if > 50 years of age. If in doubt, check FSH, LH and estradiol level) must have a negative urine or serum pregnancy test at screening.
- Sexually active patients must agree to use adequate contraception (abstinence or barrier contraceptives must be used throughout the trial and one month after end of treatment) for the duration of the study .
- Patients or their legal representative must be able to read, understand and sign an informed consent form (ICF).
- TPI 287 may interfere with coumadin dosing and patients who are taking this combination will require monitoring of their PT, PTT and international normalized ratio (INR).
Who cannot join
- Patients who are receiving concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and primidone) or who received EIAEDs within 2 weeks prior to the first dose of study drug.
- Patients with uncontrolled intracranial hypertension syndrome (defined as: persistence of headache, transient visual obscurations, and/or diplopia despite optimal clinical management) or uncontrolled seizure activity (i.e. recorded despite optimal medical management).
- Patients who are not on a stable or decreasing steroid dose for the previous week prior to the first dose of study enrollment
- Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
- Patients with an active infection (i.e., clinical signs or symptoms, including, but not limited to: bleeding/pustulant skin infections; productive cough associated with fever) on antibiotics or with a fever >/=38.5°C within 3 days prior to registration (i.e. date when the patient signs the consent and/or the patient is registered in CORE).
- Patients with New York Heart Association (NYHA) Class 3 or 4 congestive heart failure.
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- Patients with known HIV or Hepatitis B or C
- Patients who are pregnant or lactating or not practicing adequate contraception
- Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the patient's ability to sign the ICF or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results.
- Patients who are receiving concomitant systemic therapy for breast cancer.
- Patients with leptomeningeal disease (LMD) or with a history of LMD will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase 2 Open-Label Study of TPI 287 in Patients With Breast Cancer Metastatic to the Brain
The goal of the first part of this clinical research study is to find the highest tolerable dose of TPI-287 in patients with breast cancer that has spread to the brain.
The goal of the second part of this study is to learn if TPI-287 can control breast cancer that has spread to the brain. The safety of this drug will also be studied.
Read the detailed description
The Study Drug:
TPI-287 is designed to prevent cancer cells from dividing, which may slow and/or stop the growth of cancer cell.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive, TPI 287 by vein over 60 minutes on Day 1 of every 21 day cycle.
Before you receive the study drug, you will receive dexamethasone by mouth, Benadryl (diphenhydramine HCL) by vein over 30-60 minutes, and ranitidine over 30-60 minutes to help prevent a potential serious allergic reaction.
Study Visits:
At all study visits, you will be asked about any side effects you may be having and about any other drugs you may be taking.
On Days 1, 8, and 15 of Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.
On Day 1 of Cycle 1, your performance status will be recorded and your vital signs will be measured.
Within 7 days of Day 1 of Cycles 2 and beyond:
- Blood (about 2-3 tablespoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have a neurological exam.
Every 6 weeks (that is, before each odd-numbered cycle):
- You may have CT scans or MRI scans of the chest, abdomen, and pelvis to check the status of the disease.
- You will have a MRI of your brain. The MRI will require a catheter to be inserted into one of your veins in order to inject the MRI contrast agent.
The study doctor and staff will review your imaging scans to check what stage of disease the tumors inside and/or outside your brain are.
Length of Study:
You may continue to receive TPI 287 for as long as the doctor thinks it is in your best interest. You will no longer be able to receive TPI 287 if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed the end-of-treatment and follow-up visits.
End-of Treatment Visit:
About 4 weeks after you stop taking TPI 287:
- You will have a physical exam, including measurement of your vital signs.
- You will have a neurological exam.
- Your performance status will be measured.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- You will have a CT and/or MRI to check the status of the disease. This may include a brain MRI. If your doctor thinks it is needed, you will have a bone scan.
- You will be asked about any side effects you may have had any drugs you may be taking.
Follow-Up Visits:
Once you are off-study, you will be contacted either in the clinic or by phone every 3 months for up to 1 year after you enrolled on the study to check on the status of your health. If you are called, it will take less than 5 minutes.
This is an investigational study. TPI 287 is not FDA approved or commercially available. At this time, TPI 287 is being used in research only.
Up to 69 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Breast Cancer
- Being tested
- TPI 287, Dexamethasone, Benadryl, Ranitidine
- Keywords
- Breast cancer, Brain metastases, TPI 287, Computed Tomography, CT, Magnetic Resonance Imaging, MRI
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPI 287Drug
Starting dose Phase I: 160 mg/m2 by vein over 60 minutes on Days 1, 8, and 15 of every 28 day cycle.
Starting Dose Phase II: Maximum tolerated dose from Phase I.
DexamethasoneDrug
Also called Decadron
6 mg by mouth at 12 hours and 6 hours prior to treatment. As alternative and based on the treating physician discretion, dexamethasone 10 mg by vein may be given 30-60 minutes prior to treatment with TPI 287.
BenadrylDrug
Also called Diphenhydramine
12.5-25 mg intravenous (IV) push 30-60 minutes prior
RanitidineDrug
Also called Zantac, Ranitidine hydrochloride
As H2 blocker 1mg/kg IV 30-60 minutes prior
| Study group | Role | What they receive |
|---|---|---|
| TPI 287 | Experimental | TPI 287 administered at 160 mg/m2 by vein on Day 1 and repeated every three weeks. Day 1 of each subsequent cycle is equivalent of day 22 of the previous cycle; pre TPI 287: Dexamethasone 6 mg by mouth at 12 hours and 6 hours prior to treatment. As alternative and based on the treating physician discretion, Dexamethasone 10 mgby vein may be given 30-60 minutes prior to treatment with TPI 287, Benadryl 12.5-25 mg IV push over 30-60 minutes, and Ranitidine 1mg/kg IV over 30-60 minutes. Receives: Drug: TPI 287; Drug: Dexamethasone; Drug: Benadryl; Drug: Ranitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
Measured: 8-24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2011 (estimated)
- Study start16 Aug 2011
- Primary completion14 Apr 2017
- Study completion14 Apr 2017
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 M.D. Anderson 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Cortice Biosciences, Inc.
- Responsible party
- Sponsor
- Investigators
- Nuhad K. Ibrahim, MD,BS, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01332630
- Sponsor's protocol ID
- 2010-0198
- Other IDs
- NCI-2011-00929
- Status last verified
- Jun 2018
- First submitted
- 7 Apr 2011
- Last updated
- 20 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label Study of TPI 287 in Patients With Breast Cancer Metastatic to the Brain
- ClinicalTrials.gov ID
- NCT01332630
- Acronym / sponsor ID
- 2010-0198
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Brain metastases, TPI 287, Computed Tomography, CT, Magnetic Resonance Imaging, MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Cortice Biosciences, Inc.
- Study start
- 16 Aug 2011 (actual)
- Primary completion
- 14 Apr 2017 (actual)
- Study completion
- 14 Apr 2017 (actual)
- First posted
- 11 Apr 2011 (estimated)
- Results
- Posted 10 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the first part of this clinical research study is to find the highest tolerable dose of TPI-287 in patients with breast cancer that has spread to the brain.
The goal of the second part of this study is to learn if TPI-287 can control breast cancer that has spread to the brain. The safety of this drug will also be studied.
Detailed description
The Study Drug:
TPI-287 is designed to prevent cancer cells from dividing, which may slow and/or stop the growth of cancer cell.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive, TPI 287 by vein over 60 minutes on Day 1 of every 21 day cycle.
Before you receive the study drug, you will receive dexamethasone by mouth, Benadryl (diphenhydramine HCL) by vein over 30-60 minutes, and ranitidine over 30-60 minutes to help prevent a potential serious allergic reaction.
Study Visits:
At all study visits, you will be asked about any side effects you may be having and about any other drugs you may be taking.
On Days 1, 8, and 15 of Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.
On Day 1 of Cycle 1, your performance status will be recorded and your vital signs will be measured.
Within 7 days of Day 1 of Cycles 2 and beyond:
- Blood (about 2-3 tablespoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have a neurological exam.
Every 6 weeks (that is, before each odd-numbered cycle):
- You may have CT scans or MRI scans of the chest, abdomen, and pelvis to check the status of the disease.
- You will have a MRI of your brain. The MRI will require a catheter to be inserted into one of your veins in order to inject the MRI contrast agent.
The study doctor and staff will review your imaging scans to check what stage of disease the tumors inside and/or outside your brain are.
Length of Study:
You may continue to receive TPI 287 for as long as the doctor thinks it is in your best interest. You will no longer be able to receive TPI 287 if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed the end-of-treatment and follow-up visits.
End-of Treatment Visit:
About 4 weeks after you stop taking TPI 287:
- You will have a physical exam, including measurement of your vital signs.
- You will have a neurological exam.
- Your performance status will be measured.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- You will have a CT and/or MRI to check the status of the disease. This may include a brain MRI. If your doctor thinks it is needed, you will have a bone scan.
- You will be asked about any side effects you may have had any drugs you may be taking.
Follow-Up Visits:
Once you are off-study, you will be contacted either in the clinic or by phone every 3 months for up to 1 year after you enrolled on the study to check on the status of your health. If you are called, it will take less than 5 minutes.
This is an investigational study. TPI 287 is not FDA approved or commercially available. At this time, TPI 287 is being used in research only.
Up to 69 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TPI 287 | Experimental | Drug: TPI 287, Drug: Dexamethasone, Drug: Benadryl, Drug: RanitidineTPI 287 administered at 160 mg/m2 by vein on Day 1 and repeated every three weeks. Day 1 of each subsequent cycle is equivalent of day 22 of the previous cycle; pre TPI 287: Dexamethasone 6 mg by mouth at 12 hours and 6 hours prior to treatment. As alternative and based on the treating physician discretion, Dexamethasone 10 mgby vein may be given 30-60 minutes prior to treatment with TPI 287, Benadryl 12.5-25 mg IV push over 30-60 minutes, and Ranitidine 1mg/kg IV over 30-60 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically proven breast cancer with metastatic disease to the brain.
- Patients must have measurable disease on MRI that has progressed after prior therapy. PD will be defined as a>/= 25% increase in the sum of the products of greatest perpendicular diameters of all measurable disease over the smallest sum observed (since treatment started) on Gd-MRI, the appearance of new lesions on scan, or clinical or neurologic worsening despite stable disease on the last 2 scans.
- Patients may have had any number of prior surgeries, radiation and/or chemotherapy regimens as adjuvant, neoadjuvant or palliative therapy for the treatment of their disease
- Patients must be >/=18 years of age.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
Key exclusion criteria (11 listed)
- Patients who are receiving concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and primidone) or who received EIAEDs within 2 weeks prior to the first dose of study drug.
- Patients with uncontrolled intracranial hypertension syndrome (defined as: persistence of headache, transient visual obscurations, and/or diplopia despite optimal clinical management) or uncontrolled seizure activity (i.e. recorded despite optimal medical management).
- Patients who are not on a stable or decreasing steroid dose for the previous week prior to the first dose of study enrollment
- Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
- Patients with an active infection (i.e., clinical signs or symptoms, including, but not limited to: bleeding/pustulant skin infections; productive cough associated with fever) on antibiotics or with a fever >/=38.5°C within 3 days prior to registration (i.e. date when the patient signs the consent and/or the patient is registered in CORE).
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 |
|---|---|---|
| TPI 287Starting dose Phase I: 160 mg/m2 by vein over 60 minutes on Days 1, 8, and 15 of every 28 day cycle. Starting Dose Phase II: Maximum tolerated dose from Phase I. | Drug | TPI 287 |
| DexamethasoneAlso: Decadron6 mg by mouth at 12 hours and 6 hours prior to treatment. As alternative and based on the treating physician discretion, dexamethasone 10 mg by vein may be given 30-60 minutes prior to treatment with TPI 287. | Drug | TPI 287 |
| BenadrylAlso: Diphenhydramine12.5-25 mg intravenous (IV) push 30-60 minutes prior | Drug | TPI 287 |
| RanitidineAlso: Zantac, Ranitidine hydrochlorideAs H2 blocker 1mg/kg IV 30-60 minutes prior | Drug | TPI 287 |
Primary outcome
Overall Response Rate (ORR)
Time frame: 8-24 weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nuhad K. Ibrahim, MD,BS principal investigator
M.D. Anderson 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 2 study testing TPI 287, Dexamethasone and Benadryl in people with Breast Cancer, run by M.D. Anderson 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 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2018. 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 phase mean?
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 10 Jul 2018). 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?
Overall Response Rate (ORR) (time frame: 8-24 weeks). 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 20 Sep 2018.