ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

NCT00946335 | Completed Phase 1

• 4 other identifiers: NCI-2012-03177CDR649727PBTC-027U01CA081457
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of ABT-888 when given in combination with temozolomide in treating young patients with recurrent or refractory CNS tumors. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 temozolomide may kill more tumor cells.

Conditions

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Outcome Measures

Primary Outcomes (4)

• MTD or recommended phase II dose of veliparib

  28 days

• Acute toxicities

  These toxicities will be tabulated according to dose level.

  Initial 4 weeks (course 1)

• Chronic toxicities

  Tabulated according to dose level and course of therapy.

  Up to 30 days post-treatment

• Plasma drug concentrations and pharmacokinetic parameters, including volume of the central compartment (Vc/F), elimination rate constant (Ke), half-life (t1/2), apparent oral clearance (CL/F), and area under the plasma concentration time curve (AUC)

  Presented in tabular and graphical form, and estimated using compartmental methods. Dose proportionality in pharmacokinetic parameters will be investigated by performing one-way analysis of variance (ANOVA) on dose-normalized parameters.

  Baseline and during course 1

Study Arms (1)

Treatment (veliparib, temozolomide)

EXPERIMENTAL

Patients receive oral ABT-888 twice daily and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 13-26 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected for pharmacokinetics and further laboratory analysis.

Drug: veliparib; Drug: temozolomide; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

veliparib DRUG

Given PO

Also known as: ABT-888

Treatment (veliparib, temozolomide)

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Treatment (veliparib, temozolomide)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (veliparib, temozolomide)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (veliparib, temozolomide)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with a diagnosis of a primary CNS malignancy (including low-grade glioma) that is recurrent or refractory to standard therapy and for which there is no known curative therapy; all patients must have had histological verification of malignancy at initial diagnosis or relapse, excluding patients with diffuse intrinsic brain stem tumors, optic pathway tumors or CNS germ cell tumors with elevations of reliable serum or CSF tumor markers (alpha-fetoprotein or beta-HCG); patients with intrinsic pontine gliomas or optic pathway tumors do not require histological confirmation of disease but should have clinical and/or radiographic evidence of progression
• Patients must have Karnofsky Performance Score (for patients \> 16 years of age) or Lansky Performance Score (for patients =\< 16 years of age) \>= 50% assessed within two weeks of study enrollment
• Patients must be able to take oral medications (either capsules or liquid); patients with neurologic deficits must have been stable for a minimum of 1 week prior to study entry; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study; recovery is defined as all AE"s, attributable to prior therapy, having improved to grade 2 or better or as outlined below
• Myelosuppressive chemotherapy:
• Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration
• Patients must have received their last dose of nitrosourea (including Gliadel) at least six (6) weeks prior to study registration
• Biologic agent (anti-neoplastic): Patient must have received their last dose of other biologic agent ≥ 7 days prior to study registration
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
• Monoclonal antibody treatment: Patient must have received their last dose of monoclonal antibody ≥ 4 weeks prior to registration
• Radiation - Patients who have had prior radiation must have had their last fraction of:
• Craniospinal irradiation or total body irradiation \> 3 months prior to registration
• Local irradiation to the primary tumors or other sites (cumulative dose ≥ 40Gy) \> 3 months prior to registration
• Palliative irradiation delivered to symptomatic metastatic sites \> 4 weeks prior to registration
• Stem Cell Transplant: Patient must be:

You may not qualify if:

• Organ Function: Documented within 14 days of registration and within 7 days of starting treatment
• Hgb \> 8 gm/dL (transfusion independent)
• Platelet count \> 100,000/mm\^3 (transfusion independent)
• Absolute neutrophil count (ANC) \> 1, 500/mm\^3
• Total Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times institutional upper limit of normal (ULN) for age
• SGPT (ALT) ≤ 2.5 times institutional ULN for age
• Serum albumin ≥ 2 g/dL
• Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73m\^2 or a serum creatinine based on age as follows:
• ≤ 5 years - 0.8 mg/dL maximum serum creatinine
• \> 5 to ≤ 10 years - 1 mg/dL maximum serum creatinine
• \> 10 to ≤ 15 years - 1.2 mg/dL maximum serum creatinine
• \> 15 years - 1.5 maximum serum creatinine
• Patients must not be pregnant or breast-feeding; females of reproductive potential must have a negative serum or urine pregnancy test (within 72 hours prior to enrollment); males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method, which includes abstinence
• Signed informed consent which includes consent to participate in the REQUIRED pharmacokinetic and pharmacodynamic studies prior to registration
• Patients receiving any of the following medications are not eligible for study entry:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

Rhabdoid Tumor; Choroid Plexus Neoplasms; Astrocytoma; Oligodendroglioma; Familial ependymoma; Medulloblastoma; Spinal Cord Neoplasms; Optic Nerve Glioma

Interventions

veliparib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Spinal Cord Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jack Su

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2009
• First Posted: July 27, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: June 1, 2014
• Last Updated: July 9, 2014

Record last verified: 2014-06

Locations

US (1)