Safety and Efficacy Study of TPI-287 in Neuroblastoma and Medulloblastoma

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01483820
• Collaborator: Cortice Biosciences, Inc. (Industry)
• Enrollment: 8
• Locations: 8
• Arm: 1
• Duration (Months): 36
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate a new investigational drug (TPI 287) for neuroblastoma and medulloblastoma. 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, as well as the safety and tolerability of the drug.

TPI 287 was shown to be effective in stopping tumor growth and was also shown to be safe in three different animal species. TPI 287 has been tested in humans in four clinical trials, and approximately 100 subjects with various types of cancers have received the drug, including a pediatric population in our previous Phase I trial.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma; Medulloblastoma	Drug: TPI 287	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of TPI-287 in Patients With Refractory or Recurrent Neuroblastoma and Medulloblastoma
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 21-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 21-day cycle.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [length of study +30 days]

   Phase I portion of trial- To determine the safety and tolerability of TPI 287 as a single agent in pediatric and young adult patients with refractory or recurrent neuroblastoma or medulloblastoma. Adverse events collected from time of first dose to 30 days past last dose and until all related events resolved, average of one year.

Secondary Outcome Measures

1. Number of Participants With Overall Response Assessed Using RECIST Criteria [6 months]

   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.

2. Number of Days Participants Experienced Progression Free Survival (PFS) [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.

3. Median Overall Survival (OS) of Participants [3 years]

   Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)

4. Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires [3 years]

   To evaluate the impact of QOL of children receiving TPI287 using PedsQL questionnaires

5. 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]

   To evaluate the pharmacokinetics (PK) of TPI 287 in the Phase I population of this trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have histologically proven neuroblastoma or medulloblastoma and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression

• Subjects must be age >12 months and diagnosed before the age of 21

• Measurable disease, including at least one of the following:

• Measurable tumor >10mm 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

• 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 informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines

• Subjects may have received microtubulin inhibitors during previous 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 who have received any myeloablative therapy within the previous 2 months.

• Subjects receiving anti-tumor therapy for their disease or 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 patient's ability to sign or the legal guardian's ability to sign the informed consent, and patient'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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rady Children's Hospital	San Diego	California	United States	92123
2	Connecticut Children's Hospital	Hartford	Connecticut	United States	06106
3	Arnold Palmer Hospital for Children- MD Anderson	Orlando	Florida	United States	32806
4	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
5	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
6	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
7	Levine Children's Hospital	Charlotte	North Carolina	United States	28204
8	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Wake Forest University Health Sciences
• Cortice Biosciences, Inc.

Investigators

• Study Chair: Nehal Parikh, MD, Connecticut Children's Hospital
• Principal Investigator: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Beat Childhood Cancer Consortium

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01483820
• Other Study ID Numbers: NMTRC 004
• First Posted: Dec 1, 2011
• Last Update Posted: Apr 22, 2022
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Neuroblastoma; Medulloblastoma

Study Results

Participant Flow

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Period Title: Overall Study
STARTED	8
COMPLETED	0
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Overall Participants	8
Age (Count of Participants)
<=18 years	8 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%
Not Hispanic or Latino	7 87.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description	Phase I portion of trial- To determine the safety and tolerability of TPI 287 as a single agent in pediatric and young adult patients with refractory or recurrent neuroblastoma or medulloblastoma. Adverse events collected from time of first dose to 30 days past last dose and until all related events resolved, average of one year.
Time Frame	length of study +30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	8
Number [participants]	6 75%

2. Secondary Outcome

Title	Number of Participants With Overall Response Assessed Using RECIST Criteria
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	6
Number [participants]	0 0%

3. Secondary Outcome

Title	Number of Days Participants Experienced Progression Free Survival (PFS)
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	6
Number [Days]	46

4. Secondary Outcome

Title	Median Overall Survival (OS) of Participants
Description	Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	0

5. Secondary Outcome

Title	Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires
Description	To evaluate the impact of QOL of children receiving TPI287 using PedsQL questionnaires
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	0

6. Secondary Outcome

Title	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.
Description	To evaluate the pharmacokinetics (PK) of TPI 287 in the Phase I population of this trial.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
Measure Participants	0

Adverse Events

Time Frame	From date of first dose of TPI 287 until 30 days past last dose. Related AE's collected until resolution.
Arm/Group Title	TPI 287
Arm/Group Description	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 21-day cycle.
All Cause Mortality
	TPI 287
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TPI 287
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
General disorders
Progression of Disease resulting in Death	2/8 (25%)	2
Nervous system disorders
Seizure	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	TPI 287
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Blood and lymphatic system disorders
Anemia	1/8 (12.5%)	1
Hypocalcemia	1/8 (12.5%)	1
Hypokalemia	1/8 (12.5%)	1
Hypophosphatemia	1/8 (12.5%)	1
Lymphocytopenia	1/8 (12.5%)	5
Neutropenia	2/8 (25%)	2
Leukopenia	2/8 (25%)	3
Endocrine disorders
Hypoglycemia	1/8 (12.5%)	2
Gastrointestinal disorders
Diarrhea	1/8 (12.5%)	2
General disorders
fatigue	1/8 (12.5%)	1
Infusion related reaction	2/8 (25%)	2
Hepatobiliary disorders
alanine aminotransferase (ALT) increase	2/8 (25%)	2
Aspartate aminotransferase (AST) increase	1/8 (12.5%)	1
Nervous system disorders
Nervous system disorders	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.