An Efficacy Study Of Ortataxel In Recurrent Glioblastoma (Ortataxel)

Multicenter, Single Arm, Open-Label Phase II Trial On The Efficacy Of Ortataxel In Recurrent Glioblastoma

Italian Study On The Efficacy Of Ortataxel In Recurrent Glioblastoma

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Ortataxel

Detailed Description

In this phase II study, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were eligible. Patients included were treated with ortataxel 75 mg/m² i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the efficacy of ortataxel in terms of progression free survival at six months after the enrolment (PFS-6).

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Lecco, Italy
    • Ospedale di Lecco
  • Milan, Italy, 20133
    • Carlo Besta Neurological Foundation
  • Milano, Italy
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Milano, Italy
    • A.O. Ospedale Niguarda Ca' Granda
  • Pavia, Italy
    • Fondazione "Salvatore Maugeri"
  • Pavia, Italy
    • IRCCS Fondazione "Casimiro Mondino"
  • Rome, Italy
    • Istituti Fisioterapici Ospitalieri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed GBM.
• GBM in recurrence/progression after surgery (or biopsy), standard radiotherapy and chemotherapy with Temozolomide.
• Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria.
• No more than one prior line of chemotherapy (Temozolomide).
• Recovery from the toxic effects of prior therapy.

• Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:

  1. Surgery must have confirmed the recurrence.
  2. A minimum of 14 days must have elapsed from the day of surgery to registration. For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration.
  3. Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of registration.
• Age ≥ 18 years.
• Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator.
• Karnofsky-PS ≥ 60%.
• Stable or decreasing dose of corticosteroids within 5 days prior to registration.

Exclusion Criteria:

• Patients unable to undergo brain MRI scans with gadolinium (iv).
• Pre-existing peripheral neuropathy, grade ≥ 2.
• History of intracranial abscess within 6 months prior to registration.
• Anticipation of need for major surgical procedure during the course of the trial.
• Treatment with enzyme inducing antiepileptic agents was not allowed. However, patients whose anticonvulsant was changed to a nonenzymeinducing antiepileptic drug were eligible for entry after a 1-week ''washout'' period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ortataxel; 75 on day 1 every 21 days mg/m2 milligram(s)/square meter (intravenous use)	Drug: Ortataxel; 75 mg/m2, IV (in the vein) every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: IDN5109

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival-6	defined as the percentage of patients who are alive and progression free at 6 months after the randomization	after 6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	defined for each patient as the time from the date of randomization to the date of first progression, second primary malignancy or death from any cause, whichever comes first. Subjects not progressed or died at the time of the analysis will be censored at the last disease assessment date	after 9 months of follow-up for each patient
Overall survival-9	defined as the percentage of patients who are alive at 9 months after the randomization.	9 months after randomization
Objective response rate	defined as the percentage of patients who are judged by the Investigators to have an objective response as determined by the RANO criteria	after 9 months of follow-up for each patient
Number of patients with AEs, SAEs, SADRs, SUSARs	Incidence, nature, severity and seriousness of AEs, according of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0; Maximum toxicity grade experienced by each patient for each specific toxicity; Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity; Patients with at least a SAE; Patients with at least a serious adverse drug reaction (SADR); Patients with at least a suspect unexpected serious adverse reaction (SUSAR).	after 9 months of follow-up for each patient
treatment compliance	-Dose-intensity, -percentage of patients with dose and/or time modifications, - Percentage of premature withdrawals	9 months after randomization

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Antonio Silvani, MD, Fondazione IRCCS Istituto Neurologico "Carlo Besta" di Milano

Publications and helpful links

General Publications

• Silvani A, De Simone I, Fregoni V, Biagioli E, Marchioni E, Caroli M, Salmaggi A, Pace A, Torri V, Gaviani P, Quaquarini E, Simonetti G, Rulli E, D'Incalci M; Italian Association of Neuro-Oncology. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. J Neurooncol. 2019 May;142(3):455-462. doi: 10.1007/s11060-019-03116-z. Epub 2019 Feb 6.

Helpful Links

• journal article

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: October 23, 2013
• First Submitted That Met QC Criteria: November 15, 2013
• First Posted (ESTIMATE): November 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Antineoplastic Agents; IDN 5109
• Other Study ID Numbers: IRFMN-GBM-6272

Plan for Individual participant data (IPD)

Study Data/Documents

1. Clinical Study Report