NeuroblastomaPhase 1/2NCT01505608
Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma
A Phase 1/2 study testing TPI 287, Temozolomide and Irinotecan in people with Neuroblastoma, run by Giselle Sholler at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- TPI 287, Temozolomide and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 8 sitesUnited States
- Study dates
- Dec 2011to Dec 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 17Show fewer
- 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
- Subjects may have received microtubulin inhibitors during previous therapies.
- Subjects may have received any number of prior biological therapies.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Levine Children's Hospital
Charlotte, North Carolina, 28204
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, 32806
Phoenix Children's Hospital
Phoenix, Arizona
Rady Children's Hospital
San Diego, California, 92123
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
About this study
Official title: 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
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
- Being tested
- TPI 287, Temozolomide, Irinotecan
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPI 287Drug
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.
TemozolomideDrug
Also called temodar
Oral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle
IrinotecanDrug
Intravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: TPI 287; Drug: Temozolomide; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 years
Secondary outcomes (4)
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.
Measured: 1 year
Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires
Evaluate the impact on QOL of children receiving TPI+I+TMZ
Measured: 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
Measured: 3 years
Median Overall Survival (OS) of Participants
To determine OS and clinical benefit (CR/PR/SD) in this population
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2012 (estimated)
- Study startDec 2011
- Primary completionDec 2014
- Study completionDec 2014
Why it stopped: Lack of Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giselle Sholler
- Sponsor type
- University, hospital or other
- Collaborators
- Cortice Biosciences, Inc.
- Responsible party
- Sponsor-investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Don Eslin, MD, Study chair, Arnold Palmer Hospital for Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01505608
- Sponsor's protocol ID
- NMTRC 005
- Status last verified
- Aug 2024
- First submitted
- 4 Jan 2012
- Last updated
- 6 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01505608
- Acronym / sponsor ID
- NMTRC 005
- Conditions
- Neuroblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Enrollment
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Giselle ShollerUniversity, hospital or other
- Collaborators
- Cortice Biosciences, Inc.
- Study start
- Dec 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 6 Jan 2012 (estimated)
- Results
- Posted 28 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A- Temozolomide and Irinotecan | Active comparator | Drug: Temozolomide, Drug: Irinotecan1. 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. |
| Arm B- Temozolomide/Irinotecan + TPI 287 | Experimental | Drug: TPI 287, Drug: Temozolomide, Drug: IrinotecanCycle 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. |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TPI 287Subjects 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. | Drug | Arm B- Temozolomide/Irinotecan + TPI 287 |
| TemozolomideAlso: temodarOral (PO) Temozolomide at a dose of 100mg/m2 on days 1-5 of each 28 day cycle | Drug | Arm A- Temozolomide and Irinotecan, Arm B- Temozolomide/Irinotecan + TPI 287 |
| IrinotecanIntravenous (IV) Irinotecan at a dose of 10mg/m2 on days 1-5 and 8-12 of each 28 day cycle. | Drug | Arm A- Temozolomide and Irinotecan, Arm B- Temozolomide/Irinotecan + TPI 287 |
Primary outcome
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 6 months
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.
Overall Response Rate (ORR) of Participants Using RECIST Criteria
Time frame: 3 years
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.
4 secondary outcomes
Pharmacokinetics (PK) of TPI 287 in the Phase I Population of This Trial.
Time frame: 1 year
Measure Quality of Life of Children Receiving TPI287 Using PedsQL Questionnaires
Time frame: 3 years
Progression Free Survival (PFS) of Participants Using Days Until Progression
Time frame: 3 years
Median Overall Survival (OS) of Participants
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Beat Childhood CancerLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Don Eslin, MD study chair
Arnold Palmer Hospital for Children
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TPI 287, Temozolomide and Irinotecan in people with Neuroblastoma, run by Giselle Sholler at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events as a Measure of Safety and Tolerability (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.