Clinical Trials Logo

Clinical Trial Summary

RATIONALE: ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with radiation therapy and temozolomide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-888 when given together with radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed glioblastoma multiforme.


Clinical Trial Description

OBJECTIVES:

Primary

- To determine the maximum tolerated dose (MTD) of ABT-888 when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I)

- To estimate the overall survival of patients treated with ABT-888 when administered at the MTD in combination with radiotherapy and temozolomide. (Phase II)

Secondary

- To assess the toxicity associated with this regimen. (Phase I)

- To assess and describe the pharmacokinetics of ABT-888. (Phase I)

- To estimate the frequency of toxicity associated with this regimen. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of ABT-888 followed by a phase II study.

- Initiation therapy: Patients receive oral ABT-888 twice daily (once on day 1 only) and oral temozolomide once daily (beginning on day 2) in weeks 1-6. Patients enrolled in the phase I dose-escalation/phase II portion of the study also undergo concurrent radiotherapy once daily 5 days a week (beginning on day 2) in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.

- Maintenance therapy: Beginning 4 weeks after completion of initiation therapy, patients receive oral ABT-888 twice daily on days 1-7 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 4 courses (6 courses for patients enrolled in the phase I dose-escalation/phase II portion of the study) in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic, pharmacogenetic, and pharmacodynamic analysis. Samples are analyzed for concentration of ABT-888 in plasma by reversed-phase isocratic high performance liquid chromatography with electrospray ionization mass spectrometry; identification of novel markers of treatment response by plasma proteomic evaluation; DNA methylation and/or mutation; and PARP inhibition by ELISA.

After completion of study therapy, patients are followed every 2 months. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT00770471
Study type Interventional
Source Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Contact
Status Completed
Phase Phase 1
Start date July 13, 2009
Completion date March 1, 2012

See also
  Status Clinical Trial Phase
Terminated NCT00788125 - Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Phase 1/Phase 2
Completed NCT00006080 - Fenretinide in Treating Patients With Recurrent Malignant Glioma Phase 2
Recruiting NCT00887146 - Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma Phase 3
Suspended NCT00935090 - 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer N/A
Completed NCT00621686 - Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme Phase 2
Terminated NCT00227032 - Erlotinib in Treating Patients With Progressive Glioblastoma Multiforme Phase 1
Completed NCT00112502 - Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme Phase 2
Terminated NCT00243022 - Dietary, Herbal and Alternative Medicine in Glioblastoma Multiforme Phase 2
Active, not recruiting NCT00087815 - Hyperbaric Oxygen Therapy in Treating Patients With Radiation Necrosis of the Brain N/A
Active, not recruiting NCT00278278 - Combination Chemotherapy and Radiation Therapy With or Without Methotrexate in Treating Young Patients With Newly Diagnosed Gliomas Phase 3
Completed NCT00416819 - Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Primary CNS Lymphoma N/A
Completed NCT00052286 - Modafinil in Treating Fatigue and Behavioral Change in Patients With Primary Brain Cancer N/A
Completed NCT00006093 - EMD 121974 in Treating Patients With Progressive or Recurrent Glioma Phase 1/Phase 2
Recruiting NCT00004129 - Phosphorus 32 in Treating Patients With Glioblastoma Multiforme Phase 1
Completed NCT00004212 - DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas Phase 1
Completed NCT00003417 - Computer Planned Radiation Therapy Plus Chemotherapy in Treating Patients With Glioblastoma Multiforme Phase 1/Phase 2
Completed NCT00003484 - Radiolabeled Monoclonal Antibody Therapy After Radiation Therapy in Treating Patients With Primary Brain Tumors Phase 1
Completed NCT00008008 - Thiotepa Followed by Peripheral Stem Cell or Bone Marrow Transplant in Treating Patients With Malignant Glioma Phase 2
Completed NCT00003173 - High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Phase 2
Completed NCT00003464 - Temozolomide in Treating Adults With Newly Diagnosed Primary Malignant Glioblastoma Multiforme Phase 2