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

NCT01505608 | Terminated Phase 1 Results DMC

• 1 other identifier: NMTRC 005
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 8

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.

Conditions

Neuroblastoma

Outcome Measures

Primary Outcomes (2)

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

  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.

  6 months

• Overall Response Rate (ORR) of Participants Using RECIST Criteria

  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.

  3 years

Secondary Outcomes (4)

• Pharmacokinetics (PK) of TPI 287 in the Phase I Population of This Trial.

  1 year

• Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires

  3 years

• Progression Free Survival (PFS) of Participants Using Days Until Progression

  3 years

• Median Overall Survival (OS) of Participants

  3 years

Study Arms (2)

Arm A- Temozolomide and Irinotecan

ACTIVE COMPARATOR

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; Drug: Irinotecan

Arm B- Temozolomide/Irinotecan + TPI 287

EXPERIMENTAL

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; Drug: Temozolomide; Drug: Irinotecan

Interventions

TPI 287 DRUG

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.

Arm B- Temozolomide/Irinotecan + TPI 287

Temozolomide DRUG

Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle

Also known as: temodar

Arm A- Temozolomide and Irinotecan; Arm B- Temozolomide/Irinotecan + TPI 287

Irinotecan DRUG

Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.

Arm A- Temozolomide and Irinotecan; Arm B- Temozolomide/Irinotecan + 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:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (8)

Phoenix Children's Hospital

Phoenix, Arizona, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

Location

Arnold Palmer Hospital for Children- MD Anderson

Orlando, Florida, 32806, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, 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

Related Links

• Beat Childhood Cancer

MeSH Terms

Conditions

Neuroblastoma

Interventions

TPI-287; Temozolomide; Irinotecan

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Results Point of Contact

• Title: Giselle Sholler, MD
• Organization: NMTRC

genevieve.bergendahl@helendevoschildrens.org

6162670335

Study Officials

• Don Eslin, MD

  Arnold Palmer Hospital for Children

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 6, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 6, 2024
• Results First Posted: October 28, 2016

Record last verified: 2024-08

Locations

US (8)