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| Name | Class |
|---|---|
| Cortice Biosciences, Inc. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A- Temozolomide and Irinotecan | Active Comparator |
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. |
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| Arm B- Temozolomide/Irinotecan + TPI 287 | Experimental | Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of TPI 287 in the Phase I Population of This Trial. | 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. | 1 year |
| Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires |
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Inclusion Criteria:
Measurable tumor >10 mm by CT or MRI Positive bone marrow biopsy/aspirate Positive MIBG
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Don Eslin, MD | Arnold Palmer Hospital for Children | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Phoenix | Arizona | United States | |||
| Rady Children's Hospital |
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| Label | URL |
|---|---|
| Beat Childhood Cancer | View source |
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Phase 1- All patients assigned to TPI 287 group. Randomization began in Phase 2- Arm A patients were allowed to cross over to Arm B during cycles 1-6 if they experienced progression. 0 (zero) Arm A patients crossed over to Arm B on this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A- Temozolomide and Irinotecan |
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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase I |
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| Temozolomide | Drug | Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle |
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| Irinotecan | Drug | Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle. |
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Evaluate the impact on QOL of children receiving TPI+I+TMZ |
| 3 years |
| Progression Free Survival (PFS) of Participants Using Days Until Progression | 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 | 3 years |
| Median Overall Survival (OS) of Participants | To determine OS and clinical benefit (CR/PR/SD) in this population | 3 years |
| San Diego |
| California |
| 92123 |
| United States |
| Connecticut Children's Hospital | Hartford | Connecticut | 06106 | United States |
| Arnold Palmer Hospital for Children- MD Anderson | Orlando | Florida | 32806 | United States |
| Helen DeVos Children's Hospital | Grand Rapids | Michigan | 49503 | United States |
| Children's Mercy Hospitals and Clinics | Kansas City | Missouri | 64108 | United States |
| Cardinal Glennon Children's Medical Center | St Louis | Missouri | 63104 | United States |
| Levine Children's Hospital | Charlotte | North Carolina | 28204 | United States |
| FG001 | Arm B- Temozolomide/Irinotecan + TPI 287 | Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287
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. |
| COMPLETED |
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| NOT COMPLETED |
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| Phase II |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A- Temozolomide and Irinotecan |
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. |
| BG001 | Arm B- Temozolomide/Irinotecan + TPI 287 | Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287
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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Number | participants | 6 months |
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| Primary | 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. | 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). | Posted | Number | participants | 3 years |
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| Secondary | Pharmacokinetics (PK) of TPI 287 in the Phase I Population of This Trial. | 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. | PK's not run due to early closure of study. Data not collected or analyzed threfore no data exists. | Posted | 1 year |
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| Secondary | Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires | Evaluate the impact on QOL of children receiving TPI+I+TMZ | QOL's not collected due to early closure of study. Data not collected or analyzed threfore no data exists. | Posted | 3 years |
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| Secondary | Progression Free Survival (PFS) of Participants Using Days Until Progression | 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 | 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 | Posted | Number | Days | 3 years |
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| Secondary | Median Overall Survival (OS) of Participants | To determine OS and clinical benefit (CR/PR/SD) in this population | Not evaluated due to early closure. Study data does not exist. | Posted | 3 years |
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New adverse events collected from first dose of study drug to 30 days past last dose of study drug. Related adverse events followed until resolution, approximately 1 year.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TPI 287 | Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287
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. | 3 | 12 | 11 | 12 | ||
| EG001 | Phase II Arm A- Subjects That Did Not Receive TPI 287 | Cycle 1 to 6: Irinotecan and Temozolomide
| 0 | 2 | 0 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE 4.0 | Non-systematic Assessment |
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| Progression of Disease resulting in Death | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agitation | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE 4.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE 4.0 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE 4.0 | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE 4.0 | Non-systematic Assessment |
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| peripheral sensory neuropathy | Nervous system disorders | CTCAE 4.0 | Non-systematic Assessment |
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| Infusion Related Reaction | General disorders | CTCAE 4.0 | Non-systematic Assessment |
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| lymphocytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Weight loss | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| leukopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Giselle Sholler, MD | NMTRC | 6162670335 | genevieve.bergendahl@helendevoschildrens.org |
| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| C578069 | TPI-287 |
| D000077204 | Temozolomide |
| D000077146 | Irinotecan |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG001 | Phase I Patients + Phase II Assigned Arm B- Tmz +I+ TPI 287 | Cycle 1 to 6: Irinotecan and Temozolomide in combination with TPI 287
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. |
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