TPI 287 in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma

NCT00867568 | Completed Phase 1 Results DMC

• 1 other identifier: TPI-287
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

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.

Conditions

Neuroblastoma; Medulloblastoma; Relapse

Keywords

Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Medulloblastoma; Refractory Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  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

  2 years

Secondary Outcomes (5)

• Tmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing.

  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

  1 year

• Progression Free Survival (PFS) of Participants Using Days From Start of Study Drug Until Progression

  Up to 4 years

• Cmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing.

  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.

  Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose

Study Arms (1)

TPI 287

EXPERIMENTAL

Drug: TPI 287

Interventions

TPI 287 DRUG

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.

TPI 287

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Giselle Sholler: lead
• Cortice Biosciences, Inc.: collaborator

Study Sites (6)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Arnold Palmer Hospital for Children- MD Anderson

Orlando, Florida, 32806, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UVM/FAHC

Burlington, Vermont, 05401, United States

Location

Related Links

• Beat Childhood Cancer

MeSH Terms

Conditions

Neuroblastoma; Medulloblastoma; Recurrence

Interventions

TPI-287

Condition Hierarchy (Ancestors)

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Giselle Sholler, MD
• Organization: NMTRC

giselle.sholler@helendevoschildrens.org

6162670335

Study Officials

• Giselle Sholler, MD

  Beat Childhood Cancer at Atrium Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: March 23, 2009
• First Posted: March 24, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: February 1, 2016
• Last Updated: August 6, 2024
• Results First Posted: October 28, 2016

Record last verified: 2024-08

Locations

US (6)