Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT01505608
First received: January 4, 2012
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

The purpose of this research study is to evaluate a new investigational drug (TPI 287) for early relapsed neuroblastoma. 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, in combination with Irinotecan and Temozolomide versus the combination of Irinotecan and Temozolomide alone. This study will also evaluate the safety and tolerability of the study drug, TPI 287.


Condition Intervention Phase
Neuroblastoma
Drug: TPI 287
Drug: Temozolomide
Drug: Irinotecan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase I/II Trial of Irinotecan and Temozolomide Compared to Irinotecan and Temozolomide in Combination With TPI 287 in Patients With Primary Refractory or Early Relapsed Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Phase I portion of trial- To determine the safety and tolerability of TPI 287 in combination with Irinotecan and Temozolomide (TPI+I+TMZ) in pediatric and young adult patients with primary refractory or recurrent Neuroblastoma

  • Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Phase II portion of trial- To determine the ORR (complete and partial responses) in patients with relapsed or refractory neuroblastoma following treatment with I+TMZ vs. TPI+I+TMZ


Secondary Outcome Measures:
  • Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Phase I portion of trial- To determine the ORR (complete and partial responses) in patients with relapsed or refractory neuroblastoma following treatment with I+TMZ vs. TPI+I+TMZ

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Phase II portion of Trial- To monitor the safety of TPI in combination with Irinotecan and Temozolomide (TPI+I+TMZ) in pediatric and young adult patients with refractory or recurrent Neuroblastoma

  • Pharmacokinetics (PK) of TPI 287 in the Phase I population of this trial. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Measure Quality of Life of children receiving TPI287 using PedsQL questionnaires [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Evaluate the impact on QOL of children receiving TPI+I+TMZ

  • Progression Free Survival (PFS) of Participants using days until progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine PFS in this population

  • Median overall survival (OS) of Participants [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine OS and clinical benefit (CR/PR/SD) in this population

  • Assessment of pain scores in patients receiving TPI287 using Pain diaries and morphine equivalence scores [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To evaluate a descriptive assessment of pain scores in patient receiving TPI287


Estimated Enrollment: 132
Study Start Date: December 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A- Temozolomide and Irinotecan
  1. Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle.
  2. Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.

Patients who show progression on the I+TMZ arm may crossover to the I+TMZ+TPI 287 arm at anytime during cycles 1 to 6. If there is evidence of progression after completion of the I+TMZ arm (after completion of cycle 6) then the patient will have been considered to have completed therapy and is not eligible for the crossover.

Drug: Temozolomide
Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle
Other Name: temodar
Drug: Irinotecan
Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.
Experimental: Arm B- Temozolomide/Irinotecan + TPI 287

Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287

  1. Intravenous (IV) TPI 287 at a dose of 125 mg/m2 on Days 1, 8 and 15 of a 28-day cycle.
  2. Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle.
  3. Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.
Drug: 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 28-day cycle.
Drug: Temozolomide
Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle
Other Name: temodar
Drug: Irinotecan
Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.

  Eligibility

Ages Eligible for Study:   12 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have histologically proven Neuroblastoma and confirmation of primary refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression. Subjects must have primary refractory or have early relapse disease (early relapse disease is defined as having received ≤ one or two relapse therapies).
  • Subjects must be age >12 months and diagnosed before the age of 21 years
  • Measurable disease, including at least one of the following:

Measurable tumor >10 mm 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 table
  • 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 written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
  • Subjects may have received microtubulin inhibitors during previous therapies.
  • Subjects may have received any number of prior biological 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 may not have received more than 1 cycle of Irinotecan and Temozolomide as previous relapse therapy.
  • Subjects who have received any myeloablative therapy within the previous 2 months.
  • Subjects receiving 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 subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject'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.
  • Subjects who have previously been treated with TPI 287.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01505608

Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States
United States, California
Rady Children's Hospital
San Diego, California, United States, 92123
United States, Connecticut
Connecticut Children's Hospital
Hartford, Connecticut, United States, 06106
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, United States, 32806
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
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
Sponsors and Collaborators
Giselle Sholler
Cortice Biosciences, Inc.
Investigators
Study Chair: Don Eslin, MD Arnold Palmer Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Giselle Sholler, Vice Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01505608     History of Changes
Other Study ID Numbers: NMTRC 005
Study First Received: January 4, 2012
Last Updated: November 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroblastoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Dacarbazine
Irinotecan
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014