All subjects must meet the following inclusion and exclusion criteria. No exceptions will
be given. Imaging studies to establish eligibility must be done within three weeks prior to
enrollment. All other clinical evaluations to establish eligibility (except for SST2A IHC)
must be done within 7 days prior to enrollment.
1. Screening Criteria. 1.1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any
histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic
grade) that is recurrent, progressive, or refractory. Note that patients with DIPG
(based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible
with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have
histologic verification either at the time of diagnosis or recurrence, except for
patients meningioma who have not previously undergone biopsy or resection.
Note: Refractory disease is defined as the presence of persistent abnormality on
conventional MRI imaging that is further distinguished by histology (biopsy or sample
of lesion) or advanced imaging, OR as determined by the treating physician and
discussed with the primary investigator prior to enrollment.
1.2 Prior Therapy Patients must have recurred/progressed following prior standard
therapy for their tumor. Note: with meningioma, atypical meningioma, or anaplastic
meningioma must have received at least surgical resection or radiation.
1.3 Screening Consent Participant/legal guardian is willing to sign a screening
consent for DOTATATE PET imaging. The screening consent is to be obtained according to
institutional guidelines. Assent, when appropriate, will be obtained according to
institutional guidelines.
2. Eligibility Criteria.
- - Phase I Age Patient must be ≥ 4 and < 12 years of age at the time of enrollment.
Disease Status: Patients who participate in the efficacy expansion cohort must
have bi-dimensionally measurable disease, defined as at least one lesion that can
be accurately measured in at least two dimensions Patients with measurable
extraneural disease only are also eligible.
- - Phase II Age Patient must be ≥ 12 years at the time of enrollment.
3. Inclusion Criteria. 3.1Uptake on DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one
tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2
(confirmed by central radiology review).
3.2 Prior Therapy Patients must have recovered from the acute treatment related
toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior
chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to
entering this study.
3.3 Chemotherapy Patients must have received their last dose of known myelosuppressive
anticancer therapy at least 21 days prior to enrollment or at least 42 days if
nitrosourea.
3.4 Investigational/Biologic Agent. ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from
any acute toxicity potentially related to the agent and received their last dose of
the investigational or biologic agent ≥ 7 days prior to study enrollment.
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.
●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have
recovered from any acute toxicity potentially related to the agent and received their
last dose of the agent ≥ 28 days prior to study enrollment.
3.5 Radiation. Patients must have had their last fraction of:
- - Craniospinal irradiation or total body irradiation or radiation to > 50% of
pelvis > 3 months prior to enrollment.
- - Focal irradiation > 4 weeks prior to enrollment.
3.6 Stem Cell Transplant. Patient must be:
- - ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no
evidence of active graft vs. host disease.
- - ≥ 3 months since autologous stem cell transplant prior to enrollment.
3.7 Growth Factors Patients must be off all colony-forming growth factor(s) for at
least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin).
Two weeks must have elapsed if patients received long-acting formulations.
3.8 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at
least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least
24 hours.
3.9 Neurologic Status.
- - Patients with neurological deficits should have deficits that are stable for a
minimum of 1 week prior to enrollment, documented by a detailed neurological
exam.
- - Patients with seizure disorders may be enrolled if seizures are well controlled.
3.10 Performance Status Karnofsky Performance Scale (KPS for > 16 years of age) or
Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of
enrollment must be ≥ 50. Patients who are unable to walk because of neurologic
deficits, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score. 3.11 Organ Function. Patients must have adequate organ and marrow function, both for eligibility for
enrollment, and to begin each subsequent cycle of Lutathera, as defined below:
- - Adequate Bone Marrow Function as defined as:
- Absolute neutrophil count ≥ 1.0 x 109 cells/ L.
- - Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet
transfusion within 7 days)
- Hemoglobin ≥8 g/dl (may receive transfusions)
- Adequate Renal Function as defined as:
- Glomerular filtration rate (GFR) estimated by cystatin C ≥ 60ml/min/1.73 m2.
- - A serum creatinine based on (Schwartz et al.
J. Peds, 106:522, 1985)
age/gender as follows:
1 to < 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2
to < 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to
< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to
< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to
< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for
females.
≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for
females.
- - Adequate Liver Function as defined as:
- Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age.
- - AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN.
- - Coagulation parameters: INR <1.5 times ULN and aPTT <1.5 times ULN unless
patients are receiving therapeutic anticoagulation which affects these
parameters.
- - Adequate Cardiac Function as defined as:
- Ejection fraction of ≥ 55% by echocardiogram.
- - Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits
of normal (patients can be on enteral supplementation)
3.12 Corticosteroids Patients who are receiving dexamethasone must be on a stable or
decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone
dose of 2.5mg/m2/day.
3.13 Pregnancy Status Female patients of childbearing potential must have a negative
serum or urine pregnancy test within 72 hours prior to receiving the first dose of
study medication. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
3.14 Pregnancy Prevention Patients of childbearing or child fathering potential must
be willing to use a medically acceptable form of birth control, which includes
abstinence, while being treated on this study and for at least 7 months after drug
cessation in females of childbearing potential and for at least 4 months after drug
cessation in males of child fathering potential.
3.15 Informed Consent The patient or parent/guardian is able to understand the consent
and is willing to sign a written informed consent document according to institutional
guidelines.
4. Exclusion Criteria. 4.1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic
disease to bone marrow are ineligible.
4.2 Presence of bulky disease Patients with bulky disease on imaging as described
below are ineligible. Treating physicians are encouraged to request a rapid central
imaging review to confirm fulfillment of these criteria if there are questions or
concerns.
Bulky disease is defined as:
- - Tumor with evidence of clinically significant uncal herniation or midline shift.
- - Tumor with diameter of >5cm in one dimension on T2/FLAIR.
- - Tumor that in the opinion of the site investigator shows significant mass effect
in either the brain or spine.
Note that patients with metastatic or multi-focal disease (with exception of bone
marrow) are eligible as long as no sites of disease meet above criteria for bulky
disease.
4.3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown
but potential risk for adverse events in nursing infants secondary to treatment of the
mother with Lutathera.
4.4 Concurrent Illness.
- - Patients with a history of any other malignancy, except patients with a secondary
brain tumor if the patient's prior malignancy has been in remission for at least
5 years from the end of treatment.
- - Patients with any clinically significant unrelated systemic illness (serious
infections or significant cardiac, pulmonary, hepatic or other organ
dysfunction), that in the opinion of the investigator would compromise the
patient's ability to tolerate protocol therapy, put them at additional risk for
toxicity or would interfere with the study procedures or results.
- - Patients with type I diabetes.
4.5 Concomitant Medications.
- - Patients who are receiving any other anti-cancer or investigational drug therapy
are ineligible.
- - Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
4.6 Prisoners will be excluded from this study.
4.7 Inability to participate: Patients who in the opinion of the investigator are
unwilling or unable to return for required follow-up visits, obtain follow-up studies
required to assess toxicity to therapy, or adhere to drug administration plan, other
study procedures, and study restrictions.
5. Inclusion of Women and Minorities Both males and females of all races and ethnic
groups are eligible for this study.
6. Criteria to Start Treatment.
- - Subjects must start therapy within seven (7) days of enrollment.
- - Laboratory values must be no older than 7 days prior to the start of therapy.
If
a test that is repeated post enrollment and prior to the start of therapy is
outside the limits for eligibility, it must be rechecked within 48 hours prior to
the start of therapy. If rechecks are still outside the limits for eligibility,
the patient may not receive protocol therapy and will be considered off study.
