Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
Status: Recruiting
Phase: Phase 2
Diagnosis: Pediatric Brain Tumor
NCT ID: NCT01217437
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-150
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 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
Conducting Institutions:
Children's Hospital Boston, Dana-Farber Cancer Institute
Overall PI:
Susan Chi, MD,
Dana-Farber Cancer Institute
Site-responsible Investigators:
Contacts:
Dana-Farber Cancer Institute:
Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,
ctip@partners.org
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of medulloblastoma or PNET of childhood that has relapsed or become
refractory to standard chemotherapy
- 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 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 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 not have evidence of new CNS hemorrhage on baseline MRI
PATIENT CHARACTERISTICS:
- Patients must have a Lansky or Karnofsky performance status score of ≥ 50%,
corresponding to ECOG categories of 0, 1, or 2 (Karnofsky for patients > 16 years of
age and Lansky for patients ≤ 16 years of age)
- Patients must have a life expectancy of ≥ 8 weeks
- Peripheral absolute neutrophil count (ANC) ≥ 1000/μL (must not have received G-CSF
within the prior 7 days)
- Platelet count ≥ 100,000/μL (transfusion independent)
- Hemoglobin ≥ 8.0 g/dL (may receive PRBC transfusions)
- Creatinine clearance or radioisotope 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 < 1,000 mg/24 hours for patient enrollment
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
- SGPT (ALT) ≤ 3 x ULN for age
- INR/PT ≤ 1.5 x ULN
- 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
- Hypertension must be well controlled (≤ 95th percentile for age and height if patient
is ≤ 17 years) on stable doses of medication
- Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme
inducing anticonvulsants
- 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 (e.g., 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 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
- No patients with known hypersensitivity to Chinese hamster ovary cell products or
other recombinant human antibodies
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- No myelosuppressive chemotherapy within 3 weeks of entry onto this study (6 weeks if
prior nitrosourea)
- 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
- Must not have received craniospinal radiotherapy within 24 weeks prior to study entry
or involved-field radiotherapy to the local tumor (and/or tumor designated as
"measurable" for protocol purposes 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
- For autologous stem cell transplant, ≥ 3 months must have elapsed prior to study
entry
- Patients must not have previously received bevacizumab, irinotecan, temozolomide, or
other anti-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 beginning
therapy should be excluded
- Patients with an intermediate surgical procedure within 14 days prior to
beginning therapy 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 (lumbar punctures or placement
of PICC lines are not considered minor procedures and may occur at any time
prior to or during therapy)
- There should be no anticipation of need for major surgical procedures during the
course of the study
- No growth factors within 7 days of entry onto this study
- Patients who are receiving corticosteroids must be on a stable or decreasing dose for
at least 7 days
- Patients must not be currently taking NSAIDs, clopidogrel, dipyridamole, or aspirin
therapy > 81 mg/day
- No other cancer chemotherapy or immunomodulating agents are permitted (the use of
alternative or complementary therapies is discouraged)
- No concurrent radiotherapy