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Childhood Atypical Teratoid/Rhabdoid TumorPhase 1NCT00946335

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

A Phase 1 study testing veliparib, temozolomide and pharmacological study in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Germ Cell Tumor, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
veliparib, temozolomide and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
Jul 2009to Jun 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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:
  • ≥ 6 months since allogeneic stem cell transplant prior to registration
  • ≥ 3 months since autologous stem cell transplant prior to registration
  • Corticosteroids: 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 platelet 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
  • 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

Who cannot join

  • Patients receiving any of the following medications are not eligible for study entry:
  • Anti-cancer therapy
  • Investigational agents
  • Patients with any clinically significant, 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Pediatric Brain Tumor Consortium

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: A Phase I Study of ABT-888, an Oral Inhibitor of Poly (ADP-Ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors

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:

  1. 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:

  1. 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.

Being tested
veliparib, temozolomide, pharmacological study, laboratory biomarker analysis
Medical subject headings
Rhabdoid Tumor, Choroid Plexus Neoplasms, Astrocytoma, Oligodendroglioma, Familial ependymoma, Medulloblastoma, Spinal Cord Neoplasms, Optic Nerve Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • veliparibDrug

    Also called ABT-888

    Given PO

  • temozolomideDrug

    Also called SCH 52365, Temodal, Temodar, TMZ

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00946335
Study groupRoleWhat they receive
Treatment (veliparib, temozolomide)ExperimentalPatients 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.
Receives: Drug: veliparib; Drug: temozolomide; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD or recommended phase II dose of veliparib

    Measured: 28 days

  2. Acute toxicities

    These toxicities will be tabulated according to dose level.

    Measured: Initial 4 weeks (course 1)

  3. Chronic toxicities

    Tabulated according to dose level and course of therapy.

    Measured: 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.

    Measured: Baseline and during course 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionOct 2011
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00946335
Sponsor's protocol ID
NCI-2012-03177
Other IDs
NCI-2012-03177, CDR649727, PBTC-027, PBTC-027, U01CA081457
Status last verified
Jun 2014
First submitted
24 Jul 2009
Last updated
9 Jul 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing veliparib, temozolomide and pharmacological study in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Germ Cell Tumor, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD or recommended phase II dose of veliparib (time frame: 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00946335.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2014; AzTrials last refreshed its copy on 26 Oct 2026.

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