Dose-Escalation Study of TPI 287 + Avastin Followed by Randomized Study of the Same Versus Avastin for Glioblastoma

Part of paid clinical trials in Birmingham, Alabama.

Sponsor
Cortice Biosciences, Inc.
Study ID
NCT01933815
Phase
PHASE1/PHASE2
Status
Suspended

Conditions

  • Glioblastoma Multiforme

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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.
  • 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.

Study Details

This trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2). The purpose of the dose-escalation study (phase 1) is to determine 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 therapy and temozolomide (TMZ). The purpose of the randomized study (phase 2) is to determine the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.

Key Dates

First listed
Sep 2, 2013
Start date
Aug 31, 2013
Status verified
Jul 2022
Primary completion
Nov 30, 2024
Completion
May 31, 2025

Study Design

Enrollment
92 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: TPI 287 + bevacizumab
    All subjects in phase 1 \& subjects randomized to the TPI 287 + bevacizumab arm in phase 2 will be administered a 1-hour IV infusion of TPI 287 once every 3 weeks (Days 1 \& 22 of 42-day cycle) \& a 30-90 minute IV infusion of bevacizumab once every 2 weeks (Days 1, 15, \& 29). In phase 1, the dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6, while the dose of bevacizumab remains constant (10 mg/kg). The first 5 dose levels will be 140, 150, 160, 170, \& 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2. Three subjects will be treated at a dose level halfway between the dose level that exceeds the MTD and the dose level immediately prior to further refine the MTD. In phase 2, the dose of TPI 287 will be the MTD determined in phase 1, \& the dose of bevacizumab will be the same as phase 1 (10 mg/kg). Subjects may continue on treatment unless they meet one or more of the protocol discontinuation criteria.
  • Active Comparator: Bevacizumab
    All subjects randomized to the bevacizumab alone arm in phase 2 will be administered 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 bevacizumab will be 10 mg/kg. Subjects will be withdrawn from the study if they meet one or more of the discontinuation criteria outlined in the protocol; however, treatment with bevacizumab may continue under the FDA approved labeling for bevacizumab at the discretion of the subject's doctor. All subjects in phase 1 will be administered TPI 287 in combination with bevacizumab (i.e., there will be no bevacizumab alone arm during phase 1).

Primary Outcome Measure

Phase 1: Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis [ Time Frame: Continuously over study treatment through 4 weeks after last dose of study drug ]

Locations (9)

FacilityCityStateZIPSite coordinators
University of Alabama at BirminghamBirminghamAlabama35249-
Washington University School of MedicineSt LouisMissouri63110-
John Theurer Cancer Center at Hackensack University Medical CenterHackensackNew Jersey07601-
The Long Island Brain Tumor Center at Neurological Surgery, P.C.CommackNew York11725-
The Long Island Brain Tumor Center at Neurological Surgery, P.C.Lake SuccessNew York11042-
University of Rochester Medical CenterRochesterNew York14642-
The Ohio State University Wexner Medical CenterColumbusOhio43210-
Memorial Hermann HospitalHoustonTexas77030-
Swedish Neuroscience InstituteSeattleWashington98122-

Find similar trials in Birmingham, AL

By research site
University of Alabama at Birmingham· Birmingham, ALWashington University School of Medicine· St Louis, MOJohn Theurer Cancer Center at Hackensack University Medical Center· Hackensack, NJThe Long Island Brain Tumor Center at Neurological Surgery, P.C.· Commack, NYThe Long Island Brain Tumor Center at Neurological Surgery, P.C.· Lake Success, NYUniversity of Rochester Medical Center· Rochester, NY

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