TPI 287 in Breast Cancer Metastatic to the Brain

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01332630
First received: April 7, 2011
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: TPI 287
Drug: Dexamethasone
Drug: Benadryl
Drug: Ranitidine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open-Label Study of TPI 287 in Patients With Breast Cancer Metastatic to the Brain

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 69
Study Start Date: August 2011
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 index measurable lesion(s) 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 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/SGOT and ALT/SGPT </= 3X the 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 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 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 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).
  5. Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
  6. Patients with 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332630

Contacts
Contact: Nuhad K. Ibrahim, MD,BS 713-792-2817

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Cortice Biosciences, Inc.
Investigators
Principal Investigator: Nuhad K. Ibrahim, MD,BS M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01332630     History of Changes
Other Study ID Numbers: 2010-0198, NCI-2011-00929
Study First Received: April 7, 2011
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Ranitidine
Ranitidine bismuth citrate
Anti-Inflammatory Agents
Anti-Ulcer Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Histamine Agents
Histamine Antagonists
Histamine H2 Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014