Clinical Trial 18501

Cancer Type: Neurologic Oncology
Interventions:ABT-414; Placebo; Temodal (Temozolomide); Temozolomide

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:

  • Hsiang-Hsuan (Michael) Yu

Overview

Study Title

A Randomized,Placebo Controlled Phase 2b/3 Study of ABT 414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)

Summary

The main purposes of this study are to evaluate whether combining ABT-414 with usual radiation therapy (RT) and temozolomide (TMZ) treatment controls glioblastoma (GBM) better than usual RT and TMZ without ABT-414, and whether ABT-414 makes participants live longer. This study will only include people whose tumors are tested and confirmed to have Epidermal Growth Factor Receptor (EGFR) amplification. The study also plans to assess: The safety of ABT-414; How the participant¿s body handles this new drug with the combination.

Objective

Primary Objective: Phase 2b: To determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide plus adjuvant temozolomide prolongs Progression Free Survival (PFS) among subjects with newly diagnosed GBM harboring EGFR amplification. Phase 3: To determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide plus adjuvant temozolomide prolongs Overall Survival (OS) among subjects with newly diagnosed GBM harboring EGFR amplification. Secondary Objectives: To determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide plus adjuvant temozolomide improves outcomes among subjects with newly diagnosed GBM harboring EGFR amplification for the following endpoints: * PFS (secondary endpoint for Phase 3). * OS (secondary endpoint for Phase 2b). * OS for the EGFRvIII-mutated tumor subgroup. * PFS for EGFRvIII-mutated tumor subgroup. * Time to deterioration in neurocognitive functioning (Clinical Trial Battery Composite [CTB COMP]). * Time to deterioration in symptom severity score M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). * Time to deterioration in symptom interference score (MDASI-BT). Safety: * Assessment of comparative safety.

Inclusion Criteria

  • Must have a clinical diagnosis of Glioblastoma (GBM).
  • Must have a confirmed Epidermal growth factor receptor amplification in tumor tissue.
  • Must have a Karnofsky Performance Status (KPS) score of 70 - 100 (N/A to the sub-study).
  • Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
  • Must have adequate bone marrow, renal, and hepatic function (For the sub-study, participants must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).

  • Exclusion Criteria

  • Multifocal, recurrent or metastatic Glioblastoma (GBM) or gliomatosis cerebri (For the sub-study, participants can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
  • Prior chemo therapy or radiosensitizer for head and neck cancer.
  • Prior radiotherapy to the head or neck in overlap of radiation fields.
  • Prior therapy for glioblastoma or other invasive malignancy.
  • Prior, concomitant or planned treatment with NovoTumor Treatment Fields (Novo-TTF), Epidermal Growth Factor Receptor (EGFR)-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.