Trial record 1 of 1 for:    COG ACNS0821
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Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01217437
First received: October 7, 2010
Last updated: July 30, 2014
Last verified: March 2014
  Purpose

This randomized phase II trial is studying how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.


Condition Intervention Phase
Recurrent Childhood Medulloblastoma
Recurrent Childhood Pineoblastoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Drug: temozolomide
Drug: irinotecan hydrochloride
Biological: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Temozolomide With Irinotecan Versus Temozolomide, Irinotecan Plus Bevacizumab (NSC# 704865) for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, a COG Randomized Phase II Screening Trial

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival for each treatment arm [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Determined for each patient and compared across regimens using the log-rank test.


Secondary Outcome Measures:
  • Response rate for each treatment arm [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Compared by means of the exact conditional test of proportions.

  • Event-free survival [ Time Frame: From enrollment to disease progression, second malignant neoplasm, death regardless of cause, or date of last contact, whichever comes first, up to 5 years ] [ Designated as safety issue: No ]
    Estimated by Kaplan-Meier method. Determined for each patient and compared across regimens using the log-rank test.


Estimated Enrollment: 120
Study Start Date: November 2010
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (temozolomide, irinotecan hydrochloride)
Patients receive temozolomide PO and irinotecan hydrochloride IV over 90 minutes on days 1-5.
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Experimental: Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)
Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Detailed Description:

PRIMARY OBJECTIVES:

l. To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan (irinotecan hydrochloride), and bevacizumab for recurrent medulloblastoma (MB)/primitive neuroectodermal tumor (PNET) of childhood.

SECONDARY OBJECTIVES:

I. To assess the response rate for each treatment arm. II. To determine event-free survival (EFS) for each patient compared across regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive temozolomide orally (PO) and irinotecan hydrochloride IV over 90 minutes on days 1-5.

ARM II: Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
  • Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence
  • Patients must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI); diffuse leptomeningeal disease is not considered measurable
  • All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment
  • Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age)
  • Patients must have a life expectancy of >= 8 weeks
  • Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
    • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies
    • External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
    • Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry
    • Study specific limitations on prior therapy:

      • Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor
      • Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry
  • Patients must have recovered from any surgical procedure before enrolling on this study:

    • Patients with a major surgical procedure within 28 days prior to enrollment should be excluded
    • Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded
    • For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed
    • There should be no anticipation of need for major surgical procedures during the course of the study

      • Examples of major, intermediate, or minor surgical procedures:

        • Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy
        • Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy
        • Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis
    • Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy
  • Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication
  • Concomitant medications restrictions:

    • Growth factor(s): Must not have received within 7 days of entry onto this study
    • Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days
    • Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days)
  • Platelet count >= 100,000/uL (transfusion independent)
  • Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows:

    • =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
    • =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
    • =< 0.6 mg/dL (for patients aged 1 to < 2 years)
    • =< 0.8 mg/dL (for patients aged 2 to < 6 years)
    • =< 1 mg/dL (for patients aged 6 to < 10 years)
    • =< 1.2 mg/dL (for patients aged 10 to < 13 years)
    • =< 1.4 mg/dL (for female patients aged >= 13 years)
    • =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
    • =< 1.7 mg/dL (for male patients aged >= 16 years)
  • Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age
  • Central nervous system function defined as

    • Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
  • Adequate coagulation defined as

    • International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal

Exclusion Criteria:

  • Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
  • Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry
  • Patients must not have a known bleeding diathesis or coagulopathy
  • Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry
  • Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history
  • Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
  • Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
  • Patients must not have serious and inadequately controlled cardiac arrhythmia
  • Female patients who are pregnant are not eligible for this study
  • Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
  • Female patients of childbearing potential must have a negative pregnancy test
  • Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217437

  Show 141 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Adam Levy Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01217437     History of Changes
Other Study ID Numbers: NCI-2011-02605, NCI-2011-02605, CDR0000686608, COG-ACNS0821, ACNS0821, ACNS0821, U10CA098543
Study First Received: October 7, 2010
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Medulloblastoma
Pinealoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibodies
Antibodies, Monoclonal
Temozolomide
Dacarbazine
Irinotecan
Bevacizumab
Camptothecin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 31, 2014