ClinicalTrials.gov
ClinicalTrials.gov Menu

TPI 287 in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00867568
Recruitment Status : Completed
First Posted : March 24, 2009
Results First Posted : October 28, 2016
Last Update Posted : October 28, 2016
Sponsor:
Collaborator:
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

Brief Summary:

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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]
  2. 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.

  3. 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

  4. 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 ]
  5. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically proven neuroblastoma and confirmation of refractory or recurrent disease or medulloblastoma with histologic confirmation at diagnosis or at the time of recurrence/progression
  • Patients must be age >12 months and diagnosed before the age of 21
  • Life expectancy must be more than 3 months
  • If measurable disease, this must be demonstrated by residual abnormal tissue at a primary or metastatic site measuring more than 1 cm in any dimension by standardized imaging (CT or MRI). For patients with neuroblastoma who only have skeletal disease, there must be at least two persisting skeletal foci on meta-iodobenzylguanidine (MIBG) follow-up scans
  • Current disease state must be one for which there is currently no known curative therapy
  • Lansky Play Score must be more than 30 and/or ECOG performance status must be 0 to 2
  • For patients with medulloblastoma receiving steroids, the dose must be stable (i.e. not increasing) for at least one week before starting study
  • Patients without bone marrow metastases must have an ANC > 750/μl and platelet count >50,000/μl
  • Adequate liver function must be demonstrated, defined as:

    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
    • SGPT (ALT) < 10 x 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 version 3 (NCI-CTCAE V3.0 (http://ctep.cancer.gov/forms/CTCAEv3.pdf))
  • A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after the 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 can not be used, contraceptive foam with a condom is recommended
  • Informed Consent: All patients and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
  • Patients may have received microtubulin inhibitors and/or temozolomide during previous therapies

Exclusion Criteria:

  • Patients who have received any chemotherapy administered within the last 21 days
  • Patients who have received radiotherapy within the last 30 days
  • Patients who have received myeloablative therapy within the previous 3 months
  • Patients receiving anti-tumor therapy for their disease or any investigational drug concurrently
  • Patients with serious infection or a life-threatening illness (unrelated to tumor) that is > Grade 2 (NCI CTCAE V3.0), or active, serious infections requiring parenteral antibiotic therapy within 4 weeks prior to screening
  • 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
  • Patients with known hypersensitivity to any of the components of the drugs to be administered on study
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study

Information from the National Library of Medicine

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


Locations
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
UVM/FAHC
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Giselle Sholler
Cortice Biosciences, Inc.
Investigators
Study Chair: Giselle Sholler, MD The Spectrum Health Group

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT00867568     History of Changes
Other Study ID Numbers: TPI-287
First Posted: March 24, 2009    Key Record Dates
Results First Posted: October 28, 2016
Last Update Posted: October 28, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Giselle Sholler, Spectrum Health Hospitals:
Relapsed Neuroblastoma
Refractory Neuroblastoma
Relapsed Medulloblastoma
Refractory Medulloblastoma

Additional relevant MeSH terms:
Neuroblastoma
Medulloblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Glioma