Clinical trial NCT01483820: Safety and Efficacy Study of TPI-287 in Neuroblastoma and Medulloblastoma
Official title: A Phase I/II Trial of TPI-287 in Patients With Refractory or Recurrent Neuroblastoma and Medulloblastoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Neuroblastoma
Medulloblastoma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Cortice Biosciences, Inc.
First posted: 2011-12-01
Enrollment: 8
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to evaluate a new investigational drug (TPI 287) for neuroblastoma and medulloblastoma. An investigational drug is one that has not yet been approved by the Food and Drug Administration. This investigational drug is called TPI 287. This study will look at the tumor's response to the study drug, TPI 287, as well as the safety and tolerability of the drug.

TPI 287 was shown to be effective in stopping tumor growth and was also shown to be safe in three different animal species. TPI 287 has been tested in humans in four clinical trials, and approximately 100 subjects with various types of cancers have received the drug, including a pediatric population in our previous Phase I trial.


Eligibility criteria: Inclusion Criteria:

* Subjects must have histologically proven neuroblastoma or medulloblastoma and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression
* Subjects must be age \>12 months and diagnosed before the age of 21
* Measurable disease, including at least one of the following:
* Measurable tumor \>10mm 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 therapy
* 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 \>50,000/μl
* Adequate Renal Function Defined As
* Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or
* A serum creatinine based on age/gender
* 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- http://ctep.cancer.gov/forms/CTCAEv4.pdf)
* 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 informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
* Subjects may have received microtubulin inhibitors during previous therapies.

Exclusion Criteria:

* 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 who have received any myeloablative therapy within the previous 2 months.
* Subjects receiving anti-tumor therapy for their disease or 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 patient's ability to sign or the legal guardian's ability to sign the informed consent, and patient'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

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: length of study +30 days
Secondary outcomes:
measure: Number of Participants With Overall Response Assessed Using RECIST Criteria
timeFrame: 6 months
measure: Number of Days Participants Experienced Progression Free Survival (PFS)
timeFrame: 3 years
measure: Median Overall Survival (OS) of Participants
timeFrame: 3 years
measure: Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires
timeFrame: 3 years
measure: To Evaluate the Drug Levels and Pharmacokinetics (PK) of TPI 287 From Blood Samples at Multiple Time Points Within the First 24 Hours on Study.
timeFrame: 1 year
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Hospital
state: Connecticut
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children- MD Anderson
state: Florida
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Connecticut Children's Hospital
name: Nehal Parikh, MD
role: STUDY_CHAIR
affiliation: Beat Childhood Cancer at Atrium Health
name: Giselle Sholler, MD
role: PRINCIPAL_INVESTIGATOR
References: