ClinicalTrials.gg
CompletedNCT00946335Updated Jul 9, 2014

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

A Phase 1 interventional study of veliparib and temozolomide in Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Central Nervous System Germ Cell Tumor and Childhood Choroid Plexus Tumor, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2014-07-09.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
31
Allocation
Not applicable
Ages
Up to 21 Years
Sex
All
01

Study 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.

Read the detailed description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors.

II. To study the plasma pharmacokinetics (PK) of ABT-888 and PARP inhibition in peripheral blood mononuclear cells (PBMC) in order to recommend a Phase 2 dose of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors.

III. To describe the toxicities of the combination of ABT-888 and temozolomide in children with recurrent or refractory CNS tumors.

SECONDARY OBJECTIVES:

I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMC) prior to and following ABT-888 administration.

II. To assess PARP expression and/or activity in tumor tissue obtained at either initial diagnosis or relapse.

III. To determine expression and/or activity of DNA repair pathways, including MGMT and mismatch repair, in tumor tissues, when available.

IV. To document, within the confines of this phase 1 trial, radiographic tumor response to ABT-888 and temozolomide.

OUTLINE: This is a dose-escalation study of ABT-888.

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.

02

Conditions studied

  • 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
03

In context

Rhabdoid Tumor

115 studies on the registry are indexed under Rhabdoid Tumor; 23 are open to participants now.

This study's enrollment of 31 is above the median of 28 across 98 interventional studies indexed under Rhabdoid Tumor.

Browse Rhabdoid Tumor studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients with a diagnosis of a primary CNS (including low-grade glioma) that is recurrent or 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 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 sites > 4 weeks prior to registration
  • Stem Cell Transplant: Patient must be:

    • ≥ 6 months since stem cell transplant prior to registration
    • ≥ 3 months since autologous stem cell transplant prior to registration
  • : Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration
  • Growth factors:

    • Off all colony forming growth factor(s) that support or white blood cell count, number or function for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin)
    • Off Pegylated G-CSF and/or Erythropoiesis Stimulating Protein for at least 14 days prior to registration
  • Temozolomide: Patients who have received temozolomide previously are eligible for this study if they meet all other inclusion and exclusion criteria
  • Organ Function: Documented within 14 days of registration and within 7 days of starting treatment
  • > 8 gm/dL (transfusion independent)
  • Platelet count > 100,000/mm\^3 (transfusion independent)
  • (ANC) > 1, 500/mm\^3
  • Total (sum of conjugated + unconjugated) ≤ 1.5 times institutional (ULN) for age
  • (ALT) ≤ 2.5 times institutional ULN for age
  • Serum albumin ≥ 2 g/dL
  • or radioisotope ≥ 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 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 method, which includes abstinence
  • Signed which includes consent to participate in the REQUIRED pharmacokinetic and pharmacodynamic studies prior to registration

Exclusion criteria

Exclusion Criteria:

  • Patients receiving any of the following medications are not eligible for study entry:

    • Anti-cancer therapy
    • agents
  • Patients with any , unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
  • Patients with uncontrolled seizures are not eligible for study entry
  • Patients with inadequately controlled systemic hypertension (SBP and/or DBP > 95th percentile for age and height
  • Patients with a prior history of hypertensive crisis and/or hypertensive encephalopathy
  • If a BP measurement prior to registration is > 95th percentile for age and height, it must be rechecked and documented to be \< 95th percentile for age and height prior to registration; if a patient falls between the height or weight percentiles, site should average the value as appropriate; for patients ≥ 18 years the normal blood pressure should be \< 140/90 mm of Hg; patients with hypertension are eligible if their blood pressures become \< 95th percentile for age and height after anti-hypertensive medications
  • Patients with documented CNS ischemia and/or infarction, whether symptomatic or discovered incidentally without clinical symptoms, will be excluded from study participation
  • Patients with an inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
Terms in these criteria, in plain language(19)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
31 participants (actual)

Study arms

  • Experimental
    Treatment (veliparib, temozolomide)

    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

  • Given PO

    Also known as: ABT-888

  • Given PO

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

  • Otherpharmacological study

    Correlative studies

    Also known as: pharmacological studies

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. MTD or recommended phase II dose of veliparib

    Time frame: 28 days

  2. Acute toxicities

    These toxicities will be tabulated according to dose level.

    Time frame: Initial 4 weeks (course 1)

  3. Chronic toxicities

    Tabulated according to dose level and course of therapy.

    Time frame: Up to 30 days post-treatment

  4. 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.

    Time frame: Baseline and during course 1

07

Study locations

1 site
  • Pediatric Brain Tumor Consortium
    Memphis, Tennessee 38105, United States
08

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jul 2009, a primary completion of Oct 2011 and a completion of Jun 2014. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 24, 2009
First posted
Jul 27, 2009
Start
Jul 2009
Primary completionActual
Oct 2011
CompletionActual
Jun 2014
Last update
Jul 9, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 9, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00946335
Responsible party
Sponsor
First posted
Jul 27, 2009
Start date
Jul 2009
Primary completion
Oct 2011
Completion
Jun 2014
Last update
Jul 9, 2014

Study contacts

Jack Su
principal investigator · Pediatric Brain Tumor Consortium
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2014. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Veliparib

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