TPI 287 in Breast Cancer Metastatic to the Brain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01332630
Recruitment Status : Completed
First Posted : April 11, 2011
Last Update Posted : April 20, 2017
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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. The safety of this drug will also be studied.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: TPI 287 Drug: Dexamethasone Drug: Benadryl Drug: Ranitidine Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study of TPI 287 in Patients With Breast Cancer Metastatic to the Brain
Actual Study Start Date : August 16, 2011
Actual Primary Completion Date : April 14, 2017
Actual Study Completion Date : April 14, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Ranitidine

Arm Intervention/treatment
Experimental: TPI 287
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.
Drug: TPI 287

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.

Drug: 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 mg by vein may be given 30-60 minutes prior to treatment with TPI 287.
Other Name: Decadron

Drug: Benadryl
12.5-25 mg intravenous (IV) push 30-60 minutes prior
Other Name: Diphenhydramine

Drug: Ranitidine
As H2 blocker 1mg/kg IV 30-60 minutes prior
Other Names:
  • Zantac
  • Ranitidine hydrochloride

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 6 months ]
    Overall response rate (ORR = Complete Responses plus Partial Responses (CR + PR) where response rates for brain metastases evaluated by MacDonald criteria, and for extracranial disease by standard RECIST, through a combination of radiologic scans and neurological examination and MRI brain scans.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have histologically proven breast cancer with metastatic disease to the brain.
  2. 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.
  3. 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
  4. Patients must be >/=18 years of age.
  5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
  6. 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).
  7. 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.
  8. 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.
  9. 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 .
  10. Patients or their legal representative must be able to read, understand and sign an informed consent form (ICF).
  11. 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).

Exclusion Criteria:

  1. 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.
  2. 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).
  3. Patients who are not on a stable or decreasing steroid dose for the previous week prior to the first dose of study enrollment
  4. Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
  5. 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).
  6. Patients with New York Heart Association (NYHA) Class 3 or 4 congestive heart failure.
  7. Patients with known HIV or Hepatitis B or C
  8. Patients who are pregnant or lactating or not practicing adequate contraception
  9. 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.
  10. Patients who are receiving concomitant systemic therapy for breast cancer.
  11. Patients with leptomeningeal disease (LMD) or with a history of LMD will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01332630

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Cortice Biosciences, Inc.
Principal Investigator: Nuhad K. Ibrahim, MD,BS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01332630     History of Changes
Other Study ID Numbers: 2010-0198
NCI-2011-00929 ( Registry Identifier: NCI CTRP )
First Posted: April 11, 2011    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Breast cancer
Brain metastases
TPI 287
Computed Tomography
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Dexamethasone acetate
Ranitidine bismuth citrate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anesthetics, Local
Central Nervous System Depressants
Sensory System Agents