TPI 287 in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma
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|ClinicalTrials.gov Identifier: NCT00867568|
Recruitment Status : Completed
First Posted : March 24, 2009
Results First Posted : October 28, 2016
Last Update Posted : October 28, 2016
The purpose of this research study is to evaluate a new investigational drug (TPI 287) for neuroblastoma and medulloblastoma both alone and in combination with temozolomide (a currently approved drug). 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 safety and tolerability of TPI 287 both alone and in combination with temozolomide, and look to establish a safe dose of this agent. The study will also look at the tumor's response to these drugs, but this is not the primary objective of this study.
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. All of these subjects that have received TPI 287 have been adults. TPI 287 has not been tested in a pediatric population before this study.
Temozolomide was tested in recurrent neuroblastoma and showed activity in a recently published study. Preclinical studies of TPI in combination with temozolomide have shown at minimum an additive effect. The ability of temozolomide and TPI 287 to be effective in combination is suggested by these two drugs showing even greater activity when used together.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma Medulloblastoma Relapse||Drug: TPI 287||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma|
|Study Start Date :||March 2009|
|Actual Primary Completion Date :||September 2011|
|Actual Study Completion Date :||February 2016|
|Experimental: TPI 287||
Drug: TPI 287
Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]To determine the safety, tolerability and maximum tolerated dose (MTD) of TPI 287 as a single agent and collect exploratory data on the safety and tolerability of TPI 287 in combination with temozolomide (TMZ) in pediatric and young adult patients with refractory or recurrent neuroblastoma or medulloblastoma
- Tmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose ]
- Number of Patients With an Overall Response Rate (ORR) of PR or CR [ Time Frame: 1 year ]Per 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.
- Progression Free Survival (PFS) of Participants Using Days From Start of Study Drug Until Progression [ Time Frame: Up to 4 years ]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
- Cmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose ]
- AUC of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00867568
|United States, California|
|Rady Children's Hospital|
|San Diego, California, United States, 92123|
|United States, Florida|
|Arnold Palmer Hospital for Children- MD Anderson|
|Orlando, Florida, United States, 32806|
|United States, Missouri|
|Cardinal Glennon Children's Medical Center|
|St. Louis, Missouri, United States, 63104|
|United States, North Carolina|
|Levine Children's Hospital|
|Charlotte, North Carolina, United States, 28204|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|United States, Vermont|
|Burlington, Vermont, United States, 05401|
|Study Chair:||Giselle Sholler, MD||The Spectrum Health Group|