- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01483820
Safety and Efficacy Study of TPI-287 in Neuroblastoma and Medulloblastoma
A Phase I/II Trial of TPI-287 in Patients With Refractory or Recurrent Neuroblastoma and Medulloblastoma
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.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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San Diego, California, United States, 92123
- Rady Children's Hospital
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Hospital
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Florida
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Orlando, Florida, United States, 32806
- Arnold Palmer Hospital for Children- MD Anderson
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Michigan
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Grand Rapids, Michigan, United States, 49503
- Helen DeVos Children's Hospital
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Missouri
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Kansas City, Missouri, United States, 64108
- Children's Mercy Hospitals and Clinics
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Saint Louis, Missouri, United States, 63104
- Cardinal Glennon Children's Medical Center
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Children's Hospital
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: TPI 287
Subjects will receive six cycles of intravenous (IV) TPI 287 at a dose of 125 mg/m2 on Days 1, 8 and 15 of a 21-day cycle.
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Subjects will receive six cycles of intravenous (IV) TPI 287 at a dose of 125 mg/m2 on Days 1, 8 and 15 of a 21-day cycle.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: length of study +30 days
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Phase I portion of trial- To determine the safety and tolerability of TPI 287 as a single agent in pediatric and young adult patients with refractory or recurrent neuroblastoma or medulloblastoma.
Adverse events collected from time of first dose to 30 days past last dose and until all related events resolved, average of one year.
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length of study +30 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Overall Response Assessed Using RECIST Criteria
Time Frame: 6 months
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Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
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6 months
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Number of Days Participants Experienced Progression Free Survival (PFS)
Time Frame: 3 years
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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3 years
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Median Overall Survival (OS) of Participants
Time Frame: 3 years
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Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)
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3 years
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Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires
Time Frame: 3 years
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To evaluate the impact of QOL of children receiving TPI287 using PedsQL questionnaires
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3 years
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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.
Time Frame: 1 year
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To evaluate the pharmacokinetics (PK) of TPI 287 in the Phase I population of this trial.
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1 year
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Nehal Parikh, MD, Connecticut Children's Hospital
- Principal Investigator: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Medulloblastoma
- Neuroblastoma
Other Study ID Numbers
- NMTRC 004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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