Trial record 2 of 12 for:    TPI | Open Studies

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

This study is currently recruiting participants.
Verified February 2014 by Cortice Biosciences, Inc.
Sponsor:
Information provided by (Responsible Party):
Cortice Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT02047214
First received: January 24, 2014
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: TPI 287
Drug: Bevacizumab
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: Phase 2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab in Adults With Recurrent or Progressive Glioblastoma Following Bevacizumab Alone

Resource links provided by NLM:


Further study details as provided by Cortice Biosciences, Inc.:

Primary Outcome Measures:
  • 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 [ Time Frame: Continuously over study treatment through 4 weeks after last dose of study drug ] [ Designated as safety issue: Yes ]
  • MTD of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab [ Time Frame: Within 42 days of receiving the first dose of study drug ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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) [ Time Frame: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated ] [ Designated as safety issue: No ]
    The Response Assessment in Neuro-Oncology (RANO) working group recommendations for updated response criteria for high-grade gliomas ((Wen et al. 2010) will be used to determine response for this trial.


Estimated Enrollment: 18
Study Start Date: January 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TPI 287 + bevacizumab
All subjects will be administered TPI 287 as an IV infusion (1-hour target duration) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 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 levels are: 140, 150, and 160 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. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol.
Drug: TPI 287
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.
Other Names:
  • TPI-287
  • NBT 287
Drug: Bevacizumab
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.
Other Name: Avastin

Detailed Description:

This multi-center trial is a phase 2, dose-escalation study of the safety, tolerability (MTD), and efficacy of TPI 287 in combination with bevacizumab in subjects who have GBM that has progressed following prior radiation and TMZ therapy and that has progressed following prior bevacizumab therapy.

All subjects will be administered TPI 287 as an intravenous (IV) infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The subsequent cycle will start 3 weeks after the last TPI 287 infusion and 2 weeks after the last bevacizumab infusion, maintaining the once every 3 week and once every 2 week schedule, respectively.

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 initial cohort of 3 subjects will be treated at a TPI 287 dose of 140 mg/m2. The planned TPI 287 dose levels are: 140, 150, and 160 mg/m2. If dose de-escalation below the starting dose level is required, dose levels of 130 and 120 mg/m2 will be used. Twelve (12) to 18 subjects are planned for enrollment, depending on the number of subjects that experience dose limiting toxicities (DLTs) that initiate within 42 days of receiving the first dose of study drug.

Dose modifications and delays will be required as described in the protocol. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. Subjects who are discontinued prior to completing Cycle 1 for any reason other than toxicity will be replaced.

Adverse events (AEs) and concomitant medications will be monitored throughout the study. Subjects will be given a diary to record any AEs or concomitant medications taken between visits. Additional safety evaluations will include physical examination (including neurologic examination), Karnofsky performance status (KPS), weight (body surface area, BSA), vital signs, hematology, serum chemistry, and urinalysis.

Efficacy evaluations will include magnetic resonance imaging [MRI, including both pre and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (FLAIR) images], corticosteroid usage, and neurologic status (as measured by neurologic exam and KPS).

  Eligibility

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

Inclusion Criteria:

  1. Histologically proven GBM
  2. Disease progression following radiation & TMZ
  3. 1st 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.
  4. 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
  5. 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
  6. Life expectancy >12 weeks
  7. Eighteen years old or older
  8. KPS equal to or greater than 70
  9. 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:

    1. 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
    2. 4 weeks from prior cytotoxic therapy
    3. 4 weeks from prior experimental drug
    4. 2 weeks from vincristine
    5. 6 weeks from nitrosoureas
    6. 3 weeks from procarbazine
    7. 1 week for non-cytotoxic agents (e.g., interferon, tamoxifen, & cis-retinoic acid)
    8. 14 days from last dose of bevacizumab
  10. Adequate bone marrow function [absolute neutrophil count (ANC) > 1,500/mm3 & platelet count of > 100,000/mm3], adequate liver function [alanine aminotransferase (ALT) & aspartate aminotransferase (AST) <3 x upper limit normal (ULN), alkaline phosphatase <2 x ULN, & total bilirubin <1.5 mg/dL], & adequate renal function (BUN & creatinine <1.5 x ULN)
  11. Minimum hemoglobin of 9 g/dL
  12. Males & women of childbearing potential must agree to abstain from sex or use an adequate method of contraception for duration of study & for 30 days after last dose of study drug
  13. Signed & dated ICF prior to Screening evaluations

Exclusion Criteria:

  1. Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
  2. Evidence or suspicion of disease metastatic to sites remote from supratentorial brain
  3. Prior treatment with anti-vascular endothelial growth factor drugs other than bevacizumab
  4. Prior treatment with TPI 287
  5. Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
  6. 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
  7. 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.
  8. Prior taxane chemotherapy for treatment of GBM or other malignancy
  9. 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
  10. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
  11. 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:

    1. Active infection including known AIDS or Hepatitis C or with a fever ≥38.5°C within 3 days prior to study enrollment
    2. Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
    3. Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)
  12. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent subject from providing informed consent
  13. Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg)
  14. Prior history of hypertensive crisis or hypertensive encephalopathy
  15. New York Heart Association Grade II or greater congestive heart failure
  16. History of myocardial infarction or unstable angina within 6 months prior to Day 1
  17. History of stroke or transient ischemic attack within 6 months prior to Day 1
  18. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
  19. History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
  20. Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic anticoagulation)
  21. Grade 2 or higher peripheral neuropathy per NCI CTCAE
  22. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  23. Serious, non-healing wound, active ulcer, or untreated bone fracture
  24. Proteinuria as demonstrated by:

    1. Urine protein:creatinine ratio ≥ 1.0 at screening OR
    2. Urine dipstick for proteinuria ≥ 2+
  25. Known hypersensitivity to any inactive ingredient of bevacizumab
  26. Known hypersensitivity to any inactive ingredient of TPI 287
  27. Pregnancy (positive pregnancy test) or lactation
  28. Inability to comply with protocol or study procedures
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02047214

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
Contact: Thiru Pillay, RN, BSN    205-934-1842    thiru@uab.edu   
Principal Investigator: Louis B. Nabors, III, M.D.         
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Lori Cappello    551-996-5098    LCappello@HackensackUMC.org   
Principal Investigator: Samuel A. Goldlust, M.D.         
Sponsors and Collaborators
Cortice Biosciences, Inc.
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Cortice Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT02047214     History of Changes
Other Study ID Numbers: TPI-287-18
Study First Received: January 24, 2014
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cortice Biosciences, Inc.:
Glioblastoma multiforme
Glioblastoma
Radiotherapy
Temozolomide
TPI 287
Taxoid
Avastin
Bevacizumab

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014