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

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. Identifier: NCT01505608
Recruitment Status : Terminated (Lack of Enrollment)
First Posted : January 6, 2012
Results First Posted : October 28, 2016
Last Update Posted : December 2, 2020
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
Giselle SaulnierSholler, Atrium Health

Brief Summary:
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 or disease Intervention/treatment Phase
Neuroblastoma Drug: TPI 287 Drug: Temozolomide Drug: Irinotecan Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Study Start Date : December 2011
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ]

    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.

    Phase I patients were all enrolled to receive TPI 287. Phase 2 is where randomization began. Patients were different patients than the Phase 1 patients. Below all patients that received TPI 287 are included in the TPI 287 group. This includes Phase I patients and the Phase 2 patients randomized to TPI 287.

  2. Overall Response Rate (ORR) of Participants Using RECIST Criteria [ Time Frame: 3 years ]

    Phase I portion of trial- All patients enrolled to recieve TPI+I+TMZ. These patients will be added to the Phase II patients that were randomized to Arm B- Arm with TPI 287 (recieved same tx as Phase I participatns).

    Phase II portion of trial- TPatients enrolled to this portion (different patients than enrolled to Phase 1) were randomized to Arm A: I+TMZ OR Arm B: TPI+I+TMZ 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.

Secondary Outcome Measures :
  1. Pharmacokinetics (PK) of TPI 287 in the Phase I Population of This Trial. [ Time Frame: 1 year ]
    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.

  2. Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires [ Time Frame: 3 years ]
    Evaluate the impact on QOL of children receiving TPI+I+TMZ

  3. Progression Free Survival (PFS) of Participants Using Days Until Progression [ Time Frame: 3 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. Median Overall Survival (OS) of Participants [ Time Frame: 3 years ]
    To determine OS and clinical benefit (CR/PR/SD) in this population

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.

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

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-
  • 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.

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 identifier (NCT number): NCT01505608

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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
Saint Louis, Missouri, United States, 63104
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28204
Sponsors and Collaborators
Giselle SaulnierSholler
Cortice Biosciences, Inc.
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Study Chair: Don Eslin, MD Arnold Palmer Hospital for Children
Additional Information:
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Responsible Party: Giselle SaulnierSholler, Vice Study Chair, Atrium Health Identifier: NCT01505608    
Other Study ID Numbers: NMTRC 005
First Posted: January 6, 2012    Key Record Dates
Results First Posted: October 28, 2016
Last Update Posted: December 2, 2020
Last Verified: November 2020
Additional relevant MeSH terms:
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Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents