- Disease not amenable to standard treatment (nonresectable or disease present after one
or more surgeries and/or Sandostatin treatment) or subject has failed existing first
line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy.
- Participation in Iowa Neuroendocrine Tumor Registry.
- A pathologically confirmed (histology or cytology) Neuroendocrine Tumor (NET),
Neuroblastoma (NB), Pheochromocytoma (PCC), or Paraganglioma (PGL).
- For patients with measurable or evaluable disease: >50% of lesions must demonstrate
68Ga- DOTATATE uptake greater than physiologic liver uptake by visual assessment. At
least one lesion must be confirmed by conventional imaging (CT or MRI).
- For patients with measurable disease, the target lesion is one that either has never
received external beam radiation or has been previously irradiated and has since
- For patients with no measurable disease (no measurable target lesions), who have
evaluable disease (bone disease, MIBG positive disease, liver metastases not
detectable on MRI or CT), the disease must be seen on 68Ga-DOTATATE PET/CT.
- For patients with neuroblastoma, If the patient has only one MIBG positive lesion and
that lesion was radiated, a biopsy or 18FDG PET scan must be done at least 28 days
after radiation was completed and must show viable neuroblastoma. Such a lesion is not
sufficient for eligibility if no lesions are positive for 68Ga- DOTATATE PET/CT.
- No previous endogenous radiation with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC within 12
months of most recent treatment. Previous treatment must be limited to ≤40 Gy
biologically effective dose (BED) to kidneys and ≤2 Gy to bone marrow; hematopoietic
stem cells (HSC) ≥2X106 CD34+ cells/kg must be available if >2 Gy prior exposure to
- Previous treatment of neuroblastoma with 131I-MIBG must be limited to ≤40 Gy
biologically effective dose (BED) to kidneys and ≤3 Gy to bone marrow; hematopoietic
stem cells (HSC) ≥2X106 CD34+ cells/kg must be available if >3 Gy prior exposure to
- Age 18 months-18 years except neuroblastoma with amplified NMYC may be eligible at 6
- Performance status as determined by Karnofsky ≥60 or Lansky Play Scale ≥60 at the time
of study drug administration.
NOTE: Neurologic deficits in patients with brain metastases must have been stable for at
least 7 days prior to study enrollment.
- Completion of validated Pediatric Quality of Life Questionnaire.
- Within 7 days of study drug administration, must have normal organ and bone marrow
function as defined below:
Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) ≥750/mm3
- Platelet count ≥75,000/mm3 (transfusion independent, defined as not receiving platelet
transfusions for at least 7 days prior to enrollment)
- Hemoglobin ≥8g/dL
Organ Function Requirements:
- AST(SGOT)& ALT(SGPT); <10X institutional upper limit of normal for age
- Total bilirubin; <3X ULN for age
- Creatinine, BUN, potassium, sodium, chloride, bicarbonate, magnesium, phosphorus,
calcium, glucose; Normal for age
- Glomerular filtration rate (GFR); Nuclear GFR or CrCl ≥ 80 ml/min/1.73m2
- Urinalysis; No greater than 1+ hematuria or proteinuria
- The effects of 177Lu-DOTATATE on the developing human fetus are unknown. For this
reason and because Class C agents are known to be teratogenic, all subjects
capable of becoming pregnant must agree to practice a medically acceptable birth
control measure (abstinence, birth control pills, intrauterine devices, vaginal
diaphragm, vaginal sponge, or condom with spermicidal jelly) throughout the study
and for eight months following the end of the last treatment. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.
- Parent's ability to understand and the willingness to sign a written informed
consent document for children ≤7 years of age. Children ≥7 years of age will sign
assent along with parental consent or will co-sign consent with parent in
accordance with rules of the state in which treatment is received.
- Pregnant women are excluded from this study because 177Lu-DOTATATE is a Class C agent
with potential teratogenic or abortifacient effects.
- Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with 177Lu-DOTATATE, breastfeeding should be
discontinued until 3 months after the last administration of study drug.
- Major surgery within 8 weeks of study drug administration.
- External beam radiation to both kidneys (scatter doses of <500 cGy to a single kidney
or radiation to ˂50% of a single kidney is acceptable).
- Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) for this malignancy within
12 months of first study dose.
- Another investigational drug within 8 weeks of study drug administration.
- Concurrent, malignant disease for which patient is on active therapy.
- Another significant medical, psychiatric, or surgical condition which is currently
uncontrolled by treatment and which would likely affect the subject's ability to
complete this protocol.
- Subjects who have received Sandostatin LAR or long-acting lanreotide in the past 28
days must be appropriately delayed. Subjects may be maintained on short acting
octreotide during the time from last injection of long-acting somatostatin analogue
until 18-24 hrs prior to injection of study drug.
- Known antibodies to Octreotide, Lanreotide, or DOTATATE or history of allergic
reactions attributed to compounds of similar chemical or biologic composition to
- Uncontrolled illness including, but not limited to ongoing or active infection,
uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, hepatic cirrhosis or severe impairment, or psychiatric
illness/social situations that would limit compliance with study requirements.
- Corticosteroids: Patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment are not
eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days
must have elapsed since last dose of corticosteroid
- Patients who have received a prior solid organ transplantation are not eligible
- Patients will be excluded if they have a known allergy to any of the drugs used in the
- Prior Therapy:
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
At least 21 days after the last dose of cytotoxic or myelosuppressive
chemotherapy (42 days if prior nitrosourea).
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or ANC counts): ≥ 7 days after the last dose of agent.
- Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
- Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting
growth factor (e.g. Peg-Filgrastim) or 7 days for short-acting growth factor. 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 and the study-assigned Research Coordinator.
- Interleukins, Interferons and Cytokines (other than Hematopoietic Growth
Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines
(other than Hematopoietic Growth Factors)Stem cell Infusions (with or without
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell
infusion including donor lymphocyte infusion or boost infusion: ≥ 84 days after
stem cell infusion
- Evidence of GVHD.
- Autologous stem cell infusion including boost infusion: ≥ 42 days; cellular
therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g.
modified T cells, NK cells, dendritic cells, etc.).