Trial Outcomes & Findings for TPI 287 in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma (NCT NCT00867568)

Last Updated: 2024-08-06

Results Overview

To determine the safety, tolerability and maximum tolerated dose (MTD) of TPI 287 as a single agent and collect exploratory data on the safety and tolerability of TPI 287 in combination with temozolomide (TMZ) in pediatric and young adult patients with refractory or recurrent neuroblastoma or medulloblastoma

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

2 years

Results posted on

2024-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	TPI 287 TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Overall Study STARTED	18
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	TPI 287 TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Overall Study Lack of Efficacy	10
Overall Study Adverse Event	4
Overall Study Withdrawal by Subject	1

Baseline Characteristics

TPI 287 in Patients With Refractory or Recurrent Neuroblastoma or Medulloblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TPI 287 n=18 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Age, Continuous	7.5 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	TPI 287 n=18 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	14 participants

SECONDARY outcome

Timeframe: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose

Population: Six patients at the MTD dose of 125mg/m2/dose

Outcome measures

Outcome measures
Measure	TPI 287 n=6 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Tmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing.	1 hour Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: 1 year

Population: 18 subjects enrolled, one subject censored due to age, 5 subjects not evaluable. Analysis population= 12 patients.

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.

Outcome measures

Outcome measures
Measure	TPI 287 n=12 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Number of Patients With an Overall Response Rate (ORR) of PR or CR	1 participants

SECONDARY outcome

Timeframe: Up to 4 years

Population: 18 subjects enrolled, one subject censored due to age, 5 subjects not evaluable. Analysis population= 12 patients.

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

Outcome measures

Outcome measures
Measure	TPI 287 n=12 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Progression Free Survival (PFS) of Participants Using Days From Start of Study Drug Until Progression	6.2 months Interval 0.4 to 36.4

SECONDARY outcome

Timeframe: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose

Population: Six patients at the MTD dose of 125mg/m2/dose

Outcome measures

Outcome measures
Measure	TPI 287 n=6 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Cmax of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing.	3435.00 ng/ml Standard Error 872.61

SECONDARY outcome

Timeframe: Cycle 3 day 1 at Pre dose, 0 (end of infusion), 0.25, 0.5, 1, 2, 4, and 6 hours post dose

Population: Six patients at the MTD dose of 125mg/m2/dose

Outcome measures

Outcome measures
Measure	TPI 287 n=6 Participants TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
AUC of TPI 287in Pediatrics Using Pharmacokinetic (PK) Testing.	5474.90 ng*hr/mL Standard Error 684.96

Adverse Events

TPI 287

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TPI 287 n=18 participants at risk TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Nervous system disorders Seizure	5.6% 1/18 • Number of events 1 • 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.
Renal and urinary disorders Hemorrhagic Cystitis	5.6% 1/18 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progression of disease resulting in death	5.6% 1/18 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	TPI 287 n=18 participants at risk TPI 287: Three patients will be enrolled to receive single agent TPI 287 IV administered on Days 1, 8 and 15 of the first and second 28-day cycle. The starting dose of 90 mg/m2 (Dose Level 1) is 75% of the established adult MTD for this schedule in adults, which is 125 mg/m2. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Gastrointestinal disorders Abdominal distention	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders Albumin Increase	5.6% 1/18 • Number of events 1 • 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.
Hepatobiliary disorders ALT increase	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders Neutropenia	11.1% 2/18 • Number of events 2 • 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.
Gastrointestinal disorders Anorexia	11.1% 2/18 • Number of events 2 • 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.
Hepatobiliary disorders AST Increase	11.1% 2/18 • Number of events 2 • 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.
Gastrointestinal disorders Constipation	5.6% 1/18 • Number of events 1 • 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.
General disorders Dehydration	5.6% 1/18 • Number of events 1 • 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.
Gastrointestinal disorders Diarrhea	5.6% 1/18 • Number of events 1 • 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.
General disorders Drug Reaction	5.6% 1/18 • Number of events 1 • 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.
General disorders Fatigue	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders GGT Increase	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders Anemia	5.6% 1/18 • Number of events 1 • 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.
Renal and urinary disorders Hemorrhagic cystitis	5.6% 1/18 • Number of events 1 • 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.
Hepatobiliary disorders Hyperbilirubinemia	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders Hypokalemia	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders INR	5.6% 1/18 • Number of events 1 • 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.
Blood and lymphatic system disorders Leukopenia	5.6% 1/18 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Rash- Lip sore	5.6% 1/18 • Number of events 1 • 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.
Hepatobiliary disorders Liver dysfunction	5.6% 1/18 • Number of events 1 • 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.
Nervous system disorders Neuropathic pain	5.6% 1/18 • Number of events 1 • 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.
Nervous system disorders Neuropathy sensory	11.1% 2/18 • Number of events 2 • 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.
General disorders Pain	22.2% 4/18 • Number of events 4 • 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.
Nervous system disorders Seizure	5.6% 1/18 • Number of events 1 • 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.
Nervous system disorders Peripheral neuropathy	5.6% 1/18 • Number of events 1 • 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.
Renal and urinary disorders SIADH	5.6% 1/18 • Number of events 1 • 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.
Gastrointestinal disorders Vomiting	11.1% 2/18 • Number of events 2 • 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.

Additional Information

Giselle Sholler, MD

NMTRC

Phone: 6162670335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60