Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Temozolomide

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

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.

TPI 287

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

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

Don Eslin, MD

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.

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

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

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.

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.

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.

Evaluate the impact on QOL of children receiving TPI+I+TMZ

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

To determine OS and clinical benefit (CR/PR/SD) in this population

Cortice Biosciences, Inc.

Giselle Sholler

Vice Study Chair

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.

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.

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

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

Cycle 1 to 6: Irinotecan and Temozolomide

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.

Phase II Arm A- Subjects That Did Not Receive TPI 287

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.

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

Irinotecan: 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

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Giselle Sholler, MD

Arm A- TMZ + Irinotecan Only

This group includes the 8 patients enrolled to phase 1 TPI 287 portion of the study plus the 4 additional patients randomized to TPI 287 in the Phase 2 portion = 12 patients total that received TPI 287 on this study.

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

Phase I Patients + Phase II Assigned Arm B- Tmz +I+ TPI 287

8 enrolled to Phase 1: two were non-evaluable =6 move to analysis. Another 4 randomized to Arm B with TPI 287 in Phase 2=10 evaluable in TPI 287 analysis.

2 subjects were enrolled in the Phase 2 randomized portion of the trial to Arm A- without TPI 287. This makes 2 evaluable subjects in this analysis population (did not receive TPI 287).

Overall Response Rate (ORR) of Participants Using RECIST Criteria

PK's not run due to early closure of study. Data not collected or analyzed threfore no data exists.

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

QOL's not collected due to early closure of study. Data not collected or analyzed threfore no data exists.

Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires

Arm A- 2 subjects randomized to TMZ+I. Arm B- 6 evalubale patients in Phase 1 + 4 evaluable patients in Phase 2- all received TMZ+I+TPI

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

Not evaluated due to early closure. Study data does not exist.

Median Overall Survival (OS) of Participants

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.

During Phase 2- 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.

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

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

Spots Global Cancer Trial Database for Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma

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Study Description

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