Clinical Trial: Phase II NKTR-102 In Bevacizumab-Resistant High Grade Glioma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II, Single Arm, Open Label Study Of NKTR-102 In Bevacizumab-Resistant High Grade Glioma

Brief Summary:

High Grade Gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas (GBM), are the most common and most aggressive primary brain tumors. Prognosis for patients with high-grade gliomas remains poor. The estimated median survival for patients with GBM is between 12 to 18 months. Recurrence after initial therapy with temozolomide and radiation is nearly universal. Since May 2009, the majority of patients in the US with an initial recurrence of high-grade glioma receive bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), which is thought to prevent angiogenesis in these highly vascular tumors. BEV has response rates from 32-62% and has improved overall median survival in patients with recurrent high-grade gliomas1. However, the response is short lived, and nearly 100% of patients eventually progress despite bevacizumab. No chemotherapeutic agent administered following progression through bevacizumab has made a significant impact on survival. Patients progress to death within 1-5 months after resistance develops. Therefore, patients with high-grade gliomas who have progressed through bevacizumab represent a population in dire need of a feasible and tolerable treatment.

NKTR-102 is a topoisomerase I inhibitor polymer conjugate that was engineered by attaching irinotecan molecules to a polyethylene glycol (PEG) polymer using a biodegradable linker. Irinotecan released from NKTR-102 following administration is further metabolized to the active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN38), that causes DNA damage through inhibition of topoisomerase. The goal in designing NKTR-102 was to attenuate or eliminate some of the limiting side effects of irinotecan while improving efficacy by modifying the distribution of the agent within the body. The size and structure of NKTR-102 results in marked alteration in ph

Detailed Summary:
Sponsor: Lawrence Recht

Current Primary Outcome: Progression Free Survival, Assessed by Revised Assessment in Neuro-oncology (RANO) Criteria [ Time Frame: 6 weeks from first administration of NKTR-102 ]

Will be described using Kaplan-Meier estimates. The PFS probability at 6 weeks (PFS-6week) will be estimated with an 80% power and 95% confidence intervals (80% in accord with the planned alpha level, 95% for comparability with other studies, confidence intervals based on the Greenwood formula for the variance of a survival probability).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Survival From the Time of First NKTR-102 Dose for Patients With BEV-resistant Glioma Receiving NKTR-102 to Date of Death [ Time Frame: From date of first dose of NKTR-102 to date of death, assessed up to 2 years ]
    Will be described using Kaplan-Meier estimates.
  • Overall Survival From Time of Diagnosis [ Time Frame: From date of pathologic diagnosis/confirmation of high grade glioma to date of death, assessed up to 2 years. ]
    Will be described using Kaplan-Meier estimates.


Original Secondary Outcome:

  • Survival From the Time of First NKTR-102 Dose for Patients With BEV-resistant Glioma Receiving NKTR-102 to Date of Death [ Time Frame: From date of first dose of NKTR-102 to date of death, assessed up to 2 years ]
    Will be described using Kaplan-Meier estimates.
  • Overall Survival From Time of Diagnosis [ Time Frame: From date of pathologic diagnosis/confirmation of high grade glioma to date of death, assessed up to 2 years. ]
    Will be described using Kaplan-Meier estimates.
  • Safety profile of NKTR-102 in patients with high-grade glioma assessed using the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4.0) [ Time Frame: From date of first dose of NKTR-102 to date of death, assessed up to 2 years ]
    Toxicity will be tabulated by organ system and grade.


Information By: Stanford University

Dates:
Date Received: August 2, 2012
Date Started: July 2012
Date Completion:
Last Updated: January 25, 2016
Last Verified: January 2016