TPI 287 in Breast Cancer Metastatic to the Brain

NCT01332630 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0198NCI-2011-00929
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Brain metastases; TPI 287; Computed Tomography; CT; Magnetic Resonance Imaging; MRI

Outcome Measures

Primary Outcomes (1)

• 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."

  8-24 weeks

Study Arms (1)

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.

Drug: TPI 287; Drug: Dexamethasone; Drug: Benadryl; Drug: Ranitidine

Interventions

TPI 287 DRUG

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.

TPI 287

Dexamethasone DRUG

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.

Also known as: Decadron

TPI 287

Benadryl DRUG

12.5-25 mg intravenous (IV) push 30-60 minutes prior

Also known as: Diphenhydramine

TPI 287

Ranitidine DRUG

As H2 blocker 1mg/kg IV 30-60 minutes prior

Also known as: Zantac, Ranitidine hydrochloride

TPI 287

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Cortice Biosciences, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

TPI-287; Dexamethasone; Calcium Dobesilate; Diphenhydramine; Ranitidine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Ethylamines; Amines; Benzhydryl Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Ibrahim,Nuhad K.,M.D. / Breast Medical Oncology
• Organization: UT MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Nuhad K. Ibrahim, MD,BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: August 16, 2011
• Primary Completion: April 14, 2017
• Study Completion: April 14, 2017
• Last Updated: September 20, 2018
• Results First Posted: July 10, 2018

Record last verified: 2018-06

Locations

US (1)