Inclusion Criteria:
1. Age: Patients must be ≥ 12 months and ≤ 25 years of age at the time of study
enrollment.
2. Diagnosis: Patients with histologically-confirmed adamantinomatous craniopharyngioma
(ACP) Histologic confirmation of ACP may be made on solid tumor or, if no solid tumor
can be safely obtained, cyst fluid with classic ACP characteristics of thick,
cholesterol-rich, greenish-brown liquid in the context of imaging features consistent
with craniopharyngioma, including lobulated, cystic/solid mass with calcifications
that originates in the sellar/suprasellar region.
3. Disease Status: Patients must have measurable disease.
- - Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic
and/or solid recurrence or progression at least 6 months post completion of
radiation therapy.
- - Stratum 2: Patients with measurable ACP who have undergone surgery but have NOT
previously undergone irradiation (but may have received prior systemic or
intracystic therapy).
Progressive disease is allowed but not required.
4. Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for
patients ≤ 16 years of age (See Appendix I). Note: Neurologic deficits in patients
with CNS tumors must have been stable for at least 7 days prior to study enrollment.
Patients who are unable to walk because of paralysis, but who are up in a wheelchair,
will be considered ambulatory for the purpose of assessing the performance score.
5. Prior Therapy: Patients must have recovered or stabilized from the acute toxic effects
of prior treatments.
- - Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the
last (systemic or intracystic) dose of a biologic agent.
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.
- - Immunotherapy: At least 42 days after the completion of any type of systemic
immunotherapy, e.g. tumor vaccines.
- - Monoclonal antibodies: At least 21 days after the last dose of a monoclonal
antibody.
- - Radiation therapy: Patients must have had their last (conventional or
hypofractionated) fraction of: a) Focal irradiation > 6 months prior to
enrollment and b) No prior craniospinal irradiation is permitted.
- - Corticosteroids: Patients receiving dexamethasone must be on a stable or
decreasing dose for at least 1 week prior to enrollment.
- - Myelosuppressive systemic therapy: At least 21 days must have elapsed after the
last systemic myelosuppressive therapy.
- - Surgery: At least 6 weeks must have elapsed since surgery.
6. Organ Function Requirements. Adequate Bone Marrow Function Defined as:
- - Peripheral absolute neutrophil count (ANC) ≥1000/mm3.
- - Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin >8 g/dL (may be transfused)
Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope GFR > 70ml/min/1.73 m2 or.
- - 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 Defined as:
- - Total bilirubin ≤ 1.5 × institutional upper limit of normal.
- - AST (SGOT) ≤ 2.5 × institutional upper limit of normal.
- - ALT (SGPT) ≤ 2.5 × institutional upper limit of normal.
Adequate Cardiac Function Defined as:
- - Left Ventricular Ejection Fraction greater than the institutional lower limit of
normal by echocardiogram.
- - QTc ≤ 480 msec (by Bazett formula)
Adequate Neurologic Function Defined as:
- Patients with neurological deficits should have deficits that are stable for a
minimum of 1 week prior to enrollment.
- - Patients with current seizure disorders may be enrolled if seizures are
well-controlled on antiepileptic therapies.
7. Informed Consent: All patients and/or their parents or legally authorized
representatives must sign a written informed consent. Assent, when appropriate, will
be obtained according to institutional guidelines.
Exclusion Criteria:
1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on
this study due to unknown risks of fetal and teratogenic adverse events as seen in
animal/human studies. Pregnancy tests must be obtained in girls who are
post-menarchal. Males or females of reproductive potential may not participate unless
they have agreed to use an effective contraceptive method for at least 90 days after
discontinuation of drug for females and at least 60 days for males. For females of
childbearing potential, agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive methods (bilateral tubal ligation, male
sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices, and copper intrauterine devices; hormonal contraceptive methods
must be supplemented by a barrier method) and agreement to refrain from donating eggs
are required. For males of reproductive potential, agreement to remain abstinent
(refrain from heterosexual intercourse) or use a condom, and agreement to refrain from
donating sperm.
2. Gastrointestinal Disease:
- - Patients with a history of serious gastrointestinal disease, including
inflammatory bowel disease or gastrointestinal perforation.
- - Patients who are unable to swallow, retain or absorb oral medications.
3. Concomitant Medications.
- - 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.
- - Investigational Drugs: Patients who are currently receiving another
investigational drug are not eligible.
- - Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents
are not eligible.
4. Study Specific:
- - Patients who have an uncontrolled infection are not eligible.
- - Patients who have received any live or attenuated vaccinations within three
months prior to start of therapy are not eligible.
- - Any significant concurrent medical or surgical condition that would jeopardize
the patient's safety or ability to complete the study, including, but not limited
to, disease of the nervous, renal, hepatic, cardiac (such as symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia),
pulmonary, or endocrine system.
- - Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus,
Hepatitis C Virus or Tuberculosis infection are not eligible.
- - Patients who have received a prior solid organ transplantation are not eligible.
- - Patients who in the opinion of the investigator may not be able to comply with
the safety monitoring requirements of the study are not eligible.
- - Patients who have a history of alcohol, drug, or chemical abuse within 6 months
of screening.
- - Patients who have had surgery within the last 6 weeks or who have concerns for
poor postsurgical wound healing.
- - Patients who have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to tocilizumab and its excipients are
not eligible.
