Disseminated NeuroblastomaPhase 1NCT00028522
R(+)XK469 in Treating Patients With Advanced Neuroblastoma
A Phase 1 study testing R(+)XK469 in people with Disseminated Neuroblastoma and Localized Unresectable Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages 5 to 20 years
- Conditions the study is for
- Disseminated Neuroblastoma, Localized Unresectable Neuroblastoma, Recurrent Neuroblastoma
- What is being tested?
- R(+)XK469
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2001to Sep 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 5 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy
- No active brain metastases
- Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants
- Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
- More than 3 months
- WBC at least 3,000/mm^3
Show all 32Show fewer
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal (unless due to documented Gilbert's syndrome)
- Creatinine less than 1.5 times upper limit of normal
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other concurrent uncontrolled illness that would preclude study participation
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study participation
- No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
- No HIV-positive patients
- No concurrent biologic agents
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- No other concurrent chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy
- No concurrent palliative radiotherapy
- See Disease Characteristics
- Recovered from all prior therapy
- No other concurrent investigational agents
- No concurrent commercial agents or therapies directed at malignancy
- No concurrent combination anti-retroviral therapy for HIV-positive patients
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
About this study
Official title: Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma
This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.
II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.
- Determine, preliminarily, any antineoplastic activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).
SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.
- Conditions
- Disseminated Neuroblastoma, Localized Unresectable Neuroblastoma, Recurrent Neuroblastoma, Regional Neuroblastoma
- Being tested
- R(+)XK469
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R(+)XK469Drug
Also called XK469
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy) | Experimental | SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).
SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A. Receives: Drug: R(+)XK469 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.
Measured: Day 29 of course 1
DLT
Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count < 1000/mm^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL
Measured: Day 29 of course 1
Recommended phase II dose
Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.
Measured: Day 29 of course 1
Secondary outcomes (4)
Metabolism of XK469 in pediatric patients
Performed by high-performance liquid chromatography (HPLC). Plasma metabolic ratios between metabolite and XK469 concentrations will be used as an index of metabolic activity and phenotype for each patient. The modality of the frequency distribution of metabolic ratios will be also described.
Measured: Days 1-3 of course 1
Pharmacokinetics of XK469 in pediatric patients
The maximum number of samples for pharmacokinetic studies will not exceed 20. Analyzed by non compartmental method using the WinNonlin software. Parameters include the elimination rate constant, the area under the concentration vs. time curve (AUC), terminal half-life, total (nonrenal + renal) clearance, and volume of distribution at steady state. Mean, standard deviation, and coefficient of variation will be determined for each parameter.
Measured: Days 1-3 of course 1
Pharmacodynamics of XK469 in pediatric patients
Performed by correlating area under the curve (AUC) (and other parameters) of R(+)XK469 and metabolites with observed toxicities. Specifically, we will compare the AUC in those patients who experience grade >= 2 toxicity to those who experience grade < 2 toxicity using a Wilcoxon, nonparametric rank-sum test.
Measured: Continuously over the course of study treatment
Antineoplastic activity of XK469 for neuroblastoma
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Measured: Every 2 courses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startDec 2001
- Primary completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disseminated NeuroblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Susan Cohn, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028522
- Sponsor's protocol ID
- NCI-2009-00013
- Other IDs
- NCI-2009-00013, UCCRC-11108B, CDR0000739128, NCI-4570, 11108B, 4570, U01CA069852
- Status last verified
- Dec 2013
- First submitted
- 4 Jan 2002
- Last updated
- 16 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma
- ClinicalTrials.gov ID
- NCT00028522
- Acronym / sponsor ID
- NCI-2009-00013
- Conditions
- Disseminated Neuroblastoma, Localized Unresectable Neuroblastoma, Recurrent Neuroblastoma, Regional Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2001
- Primary completion
- Sep 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.
II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.
- Determine, preliminarily, any antineoplastic activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).
SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy) | Experimental | Drug: R(+)XK469SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose). SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A. |
Who may qualify
- Ages
- 5 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (32 listed)
- Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy
- No active brain metastases
- Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
- More than 3 months
- WBC at least 3,000/mm^3
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| R(+)XK469Also: XK469Given IV | Drug | Treatment (chemotherapy) |
Primary outcome
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
Time frame: Day 29 of course 1
Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.
DLT
Time frame: Day 29 of course 1
Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count < 1000/mm^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL
Recommended phase II dose
Time frame: Day 29 of course 1
Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.
4 secondary outcomes
Metabolism of XK469 in pediatric patients
Time frame: Days 1-3 of course 1
Pharmacokinetics of XK469 in pediatric patients
Time frame: Days 1-3 of course 1
Pharmacodynamics of XK469 in pediatric patients
Time frame: Continuously over the course of study treatment
Antineoplastic activity of XK469 for neuroblastoma
Time frame: Every 2 courses
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2013.
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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.
Susan Cohn principal investigator
University of Chicago Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing R(+)XK469 in people with Disseminated Neuroblastoma and Localized Unresectable Neuroblastoma, run by National Cancer Institute (NCI) at 1 site 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 32 inclusion and 0 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: finished, as of the sponsor's last update on 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma (time frame: Day 29 of course 1). The study lists 3 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 16 Dec 2013.