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Brain and Central Nervous System TumorsPhase 1/2NCT00788125

Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

A Phase 1/2 study testing carboplatin, dasatinib and etoposide phosphate in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by City of Hope Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 1 year to 25 years
What is being tested?
carboplatin, dasatinib and etoposide phosphate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
10 Sep 2008to 30 Jul 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 1 year to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant solid tumor that did not respond to or relapsed after standard first-line chemotherapy or other antineoplastic therapy (if the standard therapy for the tumor is generally recognized to be beneficial)
  • Must have been initially diagnosed with malignancy prior to 25 years of age
  • Radiographic, nuclear image, or biopsy confirmation of disease within the past 4 weeks
  • Meets one of the following criteria:
  • Phase I: Relapsed/refractory malignant solid tumor (excluding CNS tumors)
  • Patients with recurrent or metastatic disease that was completely resected just prior to study entry are eligible
  • Phase II: Patients are stratified according to one of the following diagnoses:
  • Stratum A: Relapsed sarcoma (rhabdomyosarcoma, osteosarcoma, or Ewing sarcoma)
  • Stratum B: Other relapsed solid tumors, including any of the following:
  • Other soft tissue sarcomas
  • Kidney tumors
  • Lymphoma
  • CNS tumors*
  • Other solid tumors (neuroblastoma, gonadal and germ cell tumors, liver tumors, or miscellaneous tumors)
  • Stratum C: Newly diagnosed, poor-risk metastatic sarcoma consisting of unresectable pulmonary metastases (≥ 6 nodules) and/or disease involving multiple bones or other organs NOTE: *Patients with recurrent primary CNS tumors are eligible for the phase II portion of this study provided there are no significant intratumoral bleeding toxicities seen in either COG pediatric phase I studies of dasatinib or the phase I portion of this study
  • Radiographically measurable disease (Phase II)
  • Measurable disease is not required for patients who are enrolled in the phase I portion of this study
  • No bone marrow involvement (Phase I)
  • Patients with bone marrow involvement are eligible for the phase II portion of this study provided they are not known to be refractory to red cell or platelet transfusions

PATIENT CHARACTERISTICS:

  • Lansky performance status (PS) 50-100% (patients 1-16 years of age) or Karnofsky PS 50-100% (patients > 16 years of age)
  • Life expectancy ≥ 8 weeks
  • ANC > 1,000/μL
  • Platelet count > 75,000/μL
  • Creatinine clearance or GFR ≥ 70 mL/min OR creatinine < 1.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN for age
  • SGOT or SGPT < 2.5 times ULN for age (< 5 times ULN if liver involvement by tumor)
  • Ejection fraction normal by MUGA OR shortening fraction > 28%
  • No evidence of cardiac arrhythmias requiring therapy
  • Corrected QTc interval < 450 msecs
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to comply with the safety monitoring requirements of this study
  • No uncontrolled infection
  • No swallowing dysfunction that would preclude oral medication intake
  • Gastric or jejunal tube allowed provided it is functioning
  • No history of significant bleeding disorder unrelated to cancer, including the following:
  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies)
  • Ongoing or recent (within the past 3 months) significant gastrointestinal bleeding

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from all prior therapy
  • At least 7 days since prior and no concurrent drugs known to cause Torsades de Pointes, including the following:
  • Procainamide or disopyramide
  • Amiodarone, sotalol, ibutilide, or dofetilide
  • Erythromycin or clarithromycin
  • Chlorpromazine, haloperidol, mesoridazine, or thioridazine
  • Bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosourea-containing therapy)
  • At least 3 months since prior ifosfamide, carboplatin, and/or etoposide phosphate in the exact combination and dosage as administered in this study
  • More than 7 days since prior filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11
  • More than 14 days since prior pegfilgrastim
  • More than 30 days since prior epoetin alfa
  • No prior cranial-spinal irradiation at doses > 2,400 cGy
  • No prior radiotherapy, including total-body irradiation, to > 50% of the bone marrow space
  • No other concurrent investigational drugs or anticancer agents
  • No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, felbamate, primdone, oxcarbazepine, or carbamazepine)
  • No concurrent anti-thrombotic or anti-platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, ibuprofen, or other NSAIDs)
  • No concurrent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, or voriconazole)
  • No concurrent highly active antiretroviral therapy for HIV-positive patients
  • No concurrent St. John's wort
  • No IV bisphosphonates during the first 8 weeks of dasatinib therapy

Trial locations and contacts

1 site in 1 country.

United States1 site
  • City of Hope Medical Center

    Duarte, California, 91010-3000

Other trials in United States

About this study

Official title: Dasatinib With Ifosfamide, Carboplatin, Etoposide: A Pediatric Phase I/II Trial

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with ifosfamide, carboplatin, and etoposide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of dasatinib when given together with ifosfamide, carboplatin, and etoposide and to see how well they work in treating young patients with metastatic or recurrent malignant solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose (MTD) of dasatinib when given immediately following ifosfamide, carboplatin, and etoposide phosphate (D-ICE) as a re-induction regimen in young patients with metastatic or recurrent malignant solid tumors. (Phase I)
  • To describe and define the toxicities of D-ICE in these patients. (Phase I)
  • To determine the safety and feasibility of prolonged administration of single-agent dasatinib following completion of 2-6 courses of D-ICE in these patients. (Phase I)
  • To estimate the overall survival, progression-free survival, and time to progression in patients treated with D-ICE at the MTD followed by single-agent dasatinib. (Phase II)
  • To estimate the response rate to two courses of D-ICE when given at the MTD in these patients. (Phase II)

Secondary

  • To determine the phosphotyrosine state of SRC family kinases and related signaling pathways, including FAK, STAT3, VEGFR, AKT, EGFR, KIT, EPHA2, and PDGFR, in paraffin-embedded tumor samples as measured by immunohistochemistry prior to and during treatment with dasatinib.
  • To assess gene expression profiling in fresh frozen tissue samples as measured by microarray analysis (Affymetrix GeneChips) at baseline to identify molecular signatures that may predict response to dasatinib.
  • To correlate biomarkers and molecular signatures with dasatinib dosage, toxicity, and antitumor activity.
  • To evaluate the effect of dasatinib on phosphorylation of SRC family kinases in peripheral blood mononuclear cell samples as a surrogate marker of response prior to treatment with dasatinib, at days 14-21 or when WBC ≥ 500/μL, during each treatment course, at the time of local control, and at the time of progression.

OUTLINE: This is a multicenter, phase I, dose-escalation study of dasatinib followed by a phase II study. Patients enrolled in phase II are stratified according to disease.

Patients receive D-ICE comprising oral dasatinib twice daily on days 5-21, ifosfamide IV over 1 hour and etoposide phosphate IV over 1 hour on days 1-5, and carboplatin IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy and/or surgery (consolidation therapy) after 2, 4, or 6 courses of D-ICE. After completion of consolidation therapy, patients receive oral dasatinib twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity.

Tumor tissue and peripheral blood mononuclear cell (PBMC) samples are collected periodically for correlative laboratory studies. PBMCs are analyzed by western blotting for total and phospho-SRC, phospho-FAK, and other relevant biomarkers. Tumor tissue samples are analyzed by IHC for total and phospho-SRC, phospho-FAK, phospho-STAT3, phospho-KIT, and phospho-PDGFR, EPHA2, and VEGF. Tumor tissue samples are also analyzed by microarray gene expression profiling to define a potential molecular signature or gene expression pattern that may predict response to dasatinib.

After completion of study treatment, patients are followed periodically.

Being tested
carboplatin, dasatinib, etoposide phosphate, ifosfamide, microarray analysis
Keywords
previously treated childhood rhabdomyosarcoma, metastatic childhood soft tissue sarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, metastatic osteosarcoma, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent osteosarcoma, unspecified childhood solid tumor, protocol specific, recurrent Wilms tumor and other childhood kidney tumors, recurrent neuroblastoma, stage 4S neuroblastoma, childhood extracranial germ cell tumor, childhood malignant ovarian germ cell tumor, childhood malignant testicular germ cell tumor, childhood teratoma, clear cell sarcoma of the kidney, childhood renal cell carcinoma, recurrent renal cell cancer, congenital mesoblastic nephroma
Medical subject headings
Central Nervous System Neoplasms, Kidney Neoplasms, Liver Neoplasms, Lymphoma, Neuroblastoma, Ovarian Neoplasms, Sarcoma, Testicular Germ Cell Tumor

What participants receive

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

Study groups in NCT00788125
Study groupRoleWhat they receive
Dasatinib with Ifosfamide, Carboplatin, EtoposideExperimentalNot described
Receives: Drug: carboplatin; Drug: dasatinib; Drug: etoposide phosphate; Drug: ifosfamide; Genetic: microarray analysis; Genetic: western blotting; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

What is being measured

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

  1. Maximum Administered Dose of Dasatinib (Phase I)

    This field captured the maximum dose of dasatinib administered.

    Measured: 28 days after start of 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 posted10 Nov 2008 (estimated)
  2. Study start10 Sep 2008
  3. Primary completion30 Apr 2010
  4. Study completion30 Jul 2022

Why it stopped: Terminated early due a shift in resources after lackluster performance of the drug.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Level -1: 25 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 1: 35 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 2: 50 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 3: 65 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 4: 85 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 5 (Dasatinib alone phase only): 110 mg/m\^2/dose BID PO. Sponsor withdrew support before a second level could be attempted.
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00788125
Sponsor's protocol ID
07053
Other IDs
P30CA033572, CHNMC-07053, CA180 121, CDR0000617760
Status last verified
Oct 2026
First submitted
7 Nov 2008
Last updated
4 Nov 2026
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing carboplatin, dasatinib and etoposide phosphate in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by City of Hope Medical Center 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?

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: stopped early, as of the sponsor's last update on 4 Nov 2026. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Administered Dose of Dasatinib (Phase I) (time frame: 28 days after start of course 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 4 Nov 2026.

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