A Randomized, Phase I/II Trial of Irinotecan and Temozolomide Compared to Irinotecan and Temozolomide in Combination With TPI 287 in Patients With Primary Refractory or Early Relapsed Neuroblastoma
- Subjects must have histologically proven Neuroblastoma and confirmation of primary
refractory or recurrent disease with histologic confirmation at diagnosis or at the
time of recurrence/progression. Subjects must have primary refractory or have early
relapse disease (early relapse disease is defined as having received ≤ one or two
- Subjects must be age >12 months and diagnosed before the age of 21 years
- Measurable disease, including at least one of the following:
Measurable tumor >10 mm by CT or MRI Positive bone marrow biopsy/aspirate Positive MIBG
- Current disease state must be one for which there is currently no known curative
- Lansky Play Score or Karnofsky scale must be more than 30
- Subjects without bone marrow metastases must have an ANC > 750/μl and platelet count
- Adequate Renal Function Defined As Creatinine clearance or radioisotope GFR ≥
70ml/min/1.73 m2 or
- A serum creatinine based on age/gender table
- Adequate liver function must be demonstrated, defined as:
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age SGPT (ALT) < 10 x upper limit
of normal (ULN) for age SGOT (AST) < 10x upper limit of normal (ULN) for age
- No other significant organ toxicity defined as >Grade 2 by National Cancer Institute
Common Toxicity Criteria for Adverse Events (NCI-CTCAE V4.0-
- A negative urine pregnancy test is required for female participants of child bearing
potential (≥13 years of age or after onset of menses)
- Both male and female post-pubertal study subjects need to agree to use one of the
more effective birth control methods during treatment and for six months after
treatment is stopped. These methods include total abstinence (no sex), oral
contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants
(Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of
these cannot be used, contraceptive foam with a condom is recommended.
- Informed Consent: All subjects and/or legal guardians must sign written informed
consent. Assent, when appropriate, will be obtained according to institutional
- Subjects may have received microtubulin inhibitors during previous therapies.
- Subjects may have received any number of prior biological therapies.
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are
not eligible. Subjects must have fully recovered from the effects of prior
chemotherapy (hematological and bone marrow suppression effects), generally at least
3 weeks from the most recent administration (6 weeks for nitrosoureas). Subjects may
not have received more than 1 cycle of Irinotecan and Temozolomide as previous
- Subjects who have received any myeloablative therapy within the previous 2 months.
- Subjects receiving any investigational drug concurrently
- Subjects with serious infection or a life-threatening illness (unrelated to tumor)
that is > Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring
parenteral antibiotic therapy.
- Subjects with any other medical condition, including malabsorption syndromes, mental
illness or substance abuse, deemed by the Investigator to be likely to interfere with
the interpretation of the results or which would interfere with a subject's ability
to sign or the legal guardian's ability to sign the informed consent, and subject's
ability to cooperate and participate in the study
- Subjects with known hypersensitivity to any of the components of the drugs to be
administered on study.
- Subjects who have previously been treated with TPI 287.