Safety & Efficacy Study of TPI 287 + Avastin in Adults With Glioblastoma That Progressed Following Prior Avastin Therapy

NCT02047214 | Terminated Phase 2

• 1 other identifier: TPI-287-18
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation and temozolomide (TMZ) therapy and that has progressed following prior bevacizumab therapy.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma multiforme; Glioblastoma; Radiotherapy; Temozolomide; TPI 287; Taxoid; Avastin; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis

  Continuously over study treatment through 4 weeks after last dose of study drug

• MTD of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab

  The MTD will be defined as the highest dose level achieved at which no more than 1 out of 6 subjects experienced a DLT that initiated within 42 days of receiving the first dose of study drug.

  Within 42 days of receiving the first dose of study drug

Secondary Outcomes (1)

• Efficacy of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab as measured by median progression free survival (PFS), overall response rate, & PFS rate at 4 & 6 months (PFS4 & PFS6)

  Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated

Study Arms (1)

TPI 287 + bevacizumab

EXPERIMENTAL

All subjects will be administered TPI 287 as an IV infusion (1-hour target duration) once every 3 weeks (Days 1 and 22) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29) of a 42-day cycle. The dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6 subjects, while the dose of bevacizumab remains constant (10 mg/kg). The planned dose escalation levels are 140, 160, 170, and 180 mg/m2; subsequent dose levels will be increased in increments of 10 mg/m2. If dose de-escalation below the starting dose level of 140 mg/m2 is required, dose levels of 130 and 120 mg/m2 will be used. Once the MTD is identified, 6 additional subjects will be enrolled at the MTD to better characterize the toxicity profile at this level. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol.

Drug: TPI 287; Drug: Bevacizumab

Interventions

TPI 287 DRUG

TPI 287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class. TPI 287 is an Investigational Drug.

Also known as: TPI-287, NBT 287

TPI 287 + bevacizumab

Bevacizumab DRUG

Avastin (bevacizumab) is an FDA approved drug indicated for multiple cancers, including as a single agent for GBM for adult patients with progressive disease following prior therapy. Single agent effectiveness is based on improvement in objective response rate; no data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab.

Also known as: Avastin

TPI 287 + bevacizumab

Eligibility Criteria

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

You may qualify if:

• Histologically proven GBM
• Disease progression following radiation \& TMZ
• st progression of GBM on bevacizumab-containing regimen or within 8 weeks of discontinuing bevacizumab. In either case, must have received a minimum of 8 weeks (4 infusions) of bevacizumab.
• Baseline MRI must be performed after subject signs informed consent form (ICF), within 17 days of Day 1, \& on steroid dosage that has been stable or decreasing for at least 5 days
• Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks have elapsed from date of surgery \& subject has recovered from surgery
• Life expectancy \>12 weeks
• Eighteen years old or older
• KPS equal to or greater than 70
• Recovered from toxic effects of prior therapy to \< Grade 2 toxicity per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) prior to Day 1. Minimum duration required between prior therapy \& Day 1 is:
• At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence in which case at least 4 weeks
• weeks from prior cytotoxic therapy
• weeks from prior experimental drug
• weeks from nitrosoureas
• weeks from procarbazine
• week for non-cytotoxic agents (e.g., interferon, tamoxifen, \& cis-retinoic acid)

You may not qualify if:

• Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
• Evidence or suspicion of disease metastatic to sites remote from supratentorial brain
• Prior treatment with anti-vascular endothelial growth factor (VEGF) drugs other than bevacizumab
• Prior treatment with tyrosine-kinase inhibitors targeting VEGF, platelet-derived growth factor, fibroblast growth factor, tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE-2), or angiopoietin (or their receptors)
• Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
• Prior treatment with TPI 287
• Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
• Treatment with drugs or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4 or 2C8 within 2 weeks prior to Day 1
• Received more than one course of radiation therapy or more than a total dose of 65 Gy. May have received radiosurgery as part of initial therapy; however, dose counts against total dose limit.
• Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during course of study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• Any condition, including the presence of clinically significant laboratory abnormalities, which places subject at unacceptable risk if he/she were to participate in study or confounds the ability to interpret data from study, including:
• Active infection including known AIDS or Hepatitis C or with a fever ≥38.5°C within 3 days prior to study enrollment
• Diseases or conditions that obscure toxicity or dangerously alter drug metabolism

Sponsors & Collaborators

• Cortice Biosciences, Inc.: lead

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

H Lee Moffitt Cancer Center and Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

TPI-287; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Samuel A. Goldlust, M.D.

  John Theurer Cancer Center at Hackensack University Medical Center

  PRINCIPAL INVESTIGATOR

• Louis B. Nabors, III, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Sigmund Hsu, M.D.

  Memorial Hermann Hospital

  PRINCIPAL INVESTIGATOR

• Nimish Mohile, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Solmaz Sahebjam, M.D.

  H Lee Moffitt Cancer Center and Research Institute, Inc.

  PRINCIPAL INVESTIGATOR

• Tara L. Benkers, M.D.

  Swedish Neuroscience Institute

  PRINCIPAL INVESTIGATOR

• Priya Kumthekar, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Jian Campian, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• David Schiff, M.D.

  University of Virginia Health System

  PRINCIPAL INVESTIGATOR

• Camilo E. Fadul, M.D., F.A.A.N.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Pierre Giglio, M.D.

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 28, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 31, 2018

Record last verified: 2018-01

Locations

US (11)