Recurrent NeuroblastomaPhase 1SPOC2013-001NCT02163356
Fenretinide Lym-X-Sorb + Ketoconazole + Vincristine for Recurrent or Resistant Neuroblastoma
A Phase 1 study testing Fenretinide/LXS Oral Powder, Ketoconazole and Vincristine in people with Recurrent Neuroblastoma and Neuroblastoma, run by South Plains Oncology Consortium at 4 sites in United States.
Trial summary
Currently there is no known effective treatment for recurrent or resistant neuroblastoma. Fenretinide is an anticancer agent that may work differently than standard chemotherapy. It may cause the buildup of wax-like substances in cancer cells called ceramides. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Recurrent Neuroblastoma, Neuroblastoma
- What is being tested?
- Fenretinide/LXS Oral Powder, Ketoconazole and Vincristine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2014to May 2018
- 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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosed with neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
- Patients must have high-risk neuroblastoma with at least ONE of the following:
- Recurrent/progressive disease at any time
- Refractory disease (i.e. less than a partial response to frontline therapy)
- Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow)
- Patients must have at least ONE of the following sites of disease:
Show all 40Show fewer
- Measurable tumor on MRI or CT scan or X-ray
- MIBG scan with positive uptake at minimum of one site
- Bone marrow with tumor cells seen on routine morphology
- Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
- Patients must have a performance status of 0, 1 or 2 (Appendix I). Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have a life expectancy of greater than or equal to 8 weeks
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Must not have received myelosuppressive chemotherapy and/or biologics within 3 weeks of entry onto this study (4 weeks if prior nitrosourea)
- Patients must not have received radiation for a minimum of two weeks prior
- Patients are eligible 12 weeks after autologous stem cell transplant
- Minimum of six weeks is required following prior therapeutic doses of MIBG.
- There is no limit on number of prior regimens
- Must not have received any hematopoietic growth factors within 7 days/
- Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT's were experienced. Prior therapy with other retinoids
- Patients must NOT receive other anti-cancer agents while on study
- Palliative radiation is allowed to sites that will not be used to measure response during this study
- All patients must have adequate organ function defined as:
- Hemoglobin greater than or equal to 8.0
- ANC greater than or equal to 500 (7 days after last dose of growth factor)
- Platelet count: greater than or equal to 50,000 at least one week since last platelet transfusion
- Age-adjusted serum creatinine < 1.5 x normal for age
- Patient must have normal cardiac function documented by ejection fraction (> 55%) documented by echocardiogram or radionuclide MUGA evaluation or fractional shortening ( > 27%) documented by echocardiogram and EKG must demonstrate no abnormality severe enough to justify cardiac medications and baseline QTc interval less than or equal to 450 msecs
- Total bilirubin less than or equal to 1.5 x normal for age
- SGPT (ALT) and SGOT (AST) less than or equal to 3 x normal for age
- Normal prothrombin time (PT) for age
- Baseline hepatitis titers without evidence of acute/active hepatitis
- Serum triglycerides < 300mg/dL fasting or on a random plasma test
- Serum calcium < 11.6mg/dL
- No hematuria and/or proteinuria greater than 1+ on urinalysis
- Patients with a seizure disorder are study eligible if seizures are controlled on anticonvulsants
- Normal lung function as manifested by no dyspnea at rest and no oxygen requirement
- Negative serum beta-HCG in females, and use of effective contraception in males and females of child-bearing potential, is required
- Skin toxicity no greater than grade 1
- Patients with known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration
Who cannot join
- Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
- Pregnancy or breast feeding. Due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible. Breast milk feeding by study patient is NOT allowed
- Patients with history of organ and allogeneic stem cell transplantation
- Patients with a known history of allergy to soy products
- Patients with a known history of a severe allergy or sensitivity to wheat gluten
- Patients requiring anti-arrhythmia cardiac medications are NOT eligible
Show all 13Show fewer
- Prior therapy with fenretinide, or fenretinide + ketoconazole, if DLT's were experienced
- A known history of intolerance to ketoconazole
- A known history of intolerance to vincristine
- Patients on other essential medications for which an interaction with ketoconazole can be expected and for which dose reductions to other essential medications cannot be made in a manner adequate to ensure patient safety
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
- Active hepatitis
- Baseline cardiac QTc interval > 450 msecs
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The University of Chicago Medicine Comer Children's
Chicago, Illinois, 60637
UT Southwestern Medical Center
Dallas, Texas, 75235
Cook Children's Hospital
Fort Worth, Texas, 76104
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder Plus Ketoconazole Plus Vincristine in Patients With Recurrent or Resistant Neuroblastoma (IND #68,254)
Currently there is no known effective treatment for recurrent or resistant neuroblastoma. Fenretinide is an anticancer agent that may work differently than standard chemotherapy. It may cause the buildup of wax-like substances in cancer cells called ceramides. In laboratory studies, it was found that if too much ceramide builds up in the neuroblastoma cells, they die.
Fenretinide has been given by mouth as a capsule to many people, including children. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. This means patients have to take many capsules of fenretinide by mouth several times a day. In this study, a new oral preparation of fenretinide (called 4-HPR/LXS oral powder) is being tested to see if more fenretinide can be absorbed into the body. 4-HPR/LXS oral powder has been tested previously in a limited number of both children and adult cancer patients.
Read more
Ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. Ketoconazole will be given at the same time as the fenretinide powder.
There is preclinical data that shows that combining fenretinide and vincristine prolonged survival in animal models, therefore, it is hoped that giving the vincristine with fenretinide will work better against the neuroblastoma that either drug given alone.
About 70 children with neuroblastoma have been treated with various versions of the fenretinide powder to date, including about a dozen children that also took the fenretinide powder with ketoconazole, and no toxicities have occurred that limited the dosage and no serious or unexpected side effects occurred. However, vincristine has never been given with fenretinide or fenretinide plus ketoconazole before. Vincristine has been been given before with ketoconazole to both children and adults with neuroblastomas and other cancers.
Read the detailed description
Fenretinide has been given by mouth as a capsule to many people, including children. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. This means patients have to take many capsules of fenretinide by mouth several times a day. In this study, a new oral preparation of fenretinide (called 4-HPR/LXS oral powder) is being tested to see if more fenretinide can be absorbed into the body. 4-HPR/LXS oral powder has been tested previously in a limited number of both children and adult cancer patients.
Ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. Ketoconazole will be given at the same time as the fenretinide powder.
There is preclinical data that shows that combining fenretinide and vincristine prolonged survival in animal models, therefore, it is hoped that giving the vincristine with fenretinide will work better against the neuroblastoma that either drug given alone.
About 70 children with neuroblastoma have been treated with various versions of the fenretinide powder to date, including about a dozen children that also took the fenretinide powder with ketoconazole, and no toxicities have occurred that limited the dosage and no serious or unexpected side effects occurred. However, vincristine has never been given with fenretinide or fenretinide plus ketoconazole before. Vincristine has been been given before with ketoconazole to both children and adults with neuroblastomas and other cancers.
- Conditions
- Recurrent Neuroblastoma, Neuroblastoma
- Being tested
- Fenretinide/LXS Oral Powder, Ketoconazole, Vincristine
- Keywords
- neuroblastoma, recurrent, resistant
- Medical subject headings
- Neuroblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenretinide/LXS Oral PowderDrug
Also called 4-HPR, Fenretinide/Lym-X-Sorb, 4-HPR/LXS
Oral Powder
KetoconazoleDrug
Also called Nizoral
Oral Tablet
VincristineDrug
Also called Oncovin, Vincristine Sulfate
IV
| Study group | Role | What they receive |
|---|---|---|
| Primary therapy | Experimental | Fenretinide/LXS oral powder 1500 mg/m2/day for 7 days plus ketoconazole 6 mg/kg/day for 7 days plus single dose vincristine (dose escalating) given on day 3. Starting dose of vincristine is 0.75 mg/m2/dose. Followed by 14 days of rest. Receives: Drug: Fenretinide/LXS Oral Powder; Drug: Ketoconazole; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To determine maximum dose of vincristine when given in combination with 4-HPR/LXS and ketoconazole. Subjects will be enrolled in a standard 3 + 3 design and will receive set doses of HPR/LXS and ketoconazole. Vincristine will be escalated with each dose level up to 1.5 mg/m2. If toxicity occurs due to vincristine, the dose level will be expanded or dose decreased to the previous level as appropriate. If toxicity occurs due to ketoconazole, the dose level will be expanded and the ketoconazole dose decreased to 3 mg/kg/day
Measured: after each subject has completed 1 cycle of therapy (a cycle is 21 days)
Side effect profile of drug combination
The side effect profile of the combination therapy will be compared to known single agent side effects looking for new unique drug interactions.
Measured: after each subject receives the drug combination (a cycle is expected to be 21 days)
Assess plasma pharmacokinetics of fenretinide
included analysis of metabolites (4-MPR and 4-oxo-HPR) and related plasma sphingolipids
Measured: On day 1 (hour 0, 2, 4, 6), day 7 (hour 0, 2, 4, 6) and day 9 (after 3 pm) for course 1. For courses 2 and 6, day 1 (hour 0, 4 and 6), and day 7 (hour 0, 4, and 6)
Secondary outcomes (1)
Disease response
within limitations of a phase 1 study. Time frame may be longer if a subject receives more than 6 cycles of therapy.
Measured: every 42 days while on therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2014 (estimated)
- Study startMay 2014
- Primary completionMay 2018
- Study completionMay 2018
Why it stopped: drug supply
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- South Plains Oncology Consortium
- Sponsor type
- Research network
- Collaborators
- The Evan Foundation
- Responsible party
- Sponsor
- Investigators
- Tanya Watt, MD, Study chair, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02163356
- Sponsor's protocol ID
- SPOC-2013-001
- Acronym
- SPOC2013-001
- Status last verified
- Mar 2022
- First submitted
- 27 May 2014
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder Plus Ketoconazole Plus Vincristine in Patients With Recurrent or Resistant Neuroblastoma (IND #68,254)
- ClinicalTrials.gov ID
- NCT02163356
- Acronym / sponsor ID
- SPOC2013-001 / SPOC-2013-001
- Conditions
- Recurrent Neuroblastoma, Neuroblastoma
- Keywords
- neuroblastoma, recurrent, resistant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: drug supply
- Enrolment
- 4 participants (actual)
- Lead sponsor
- South Plains Oncology ConsortiumResearch network
- Collaborators
- The Evan Foundation
- Study start
- May 2014 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 13 Jun 2014 (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.
Currently there is no known effective treatment for recurrent or resistant neuroblastoma. Fenretinide is an anticancer agent that may work differently than standard chemotherapy. It may cause the buildup of wax-like substances in cancer cells called ceramides. In laboratory studies, it was found that if too much ceramide builds up in the neuroblastoma cells, they die.
Fenretinide has been given by mouth as a capsule to many people, including children. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. This means patients have to take many capsules of fenretinide by mouth several times a day. In this study, a new oral preparation of fenretinide (called 4-HPR/LXS oral powder) is being tested to see if more fenretinide can be absorbed into the body. 4-HPR/LXS oral powder has been tested previously in a limited number of both children and adult cancer patients.
Ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. Ketoconazole will be given at the same time as the fenretinide powder.
There is preclinical data that shows that combining fenretinide and vincristine prolonged survival in animal models, therefore, it is hoped that giving the vincristine with fenretinide will work better against the neuroblastoma that either drug given alone.
About 70 children with neuroblastoma have been treated with various versions of the fenretinide powder to date, including about a dozen children that also took the fenretinide powder with ketoconazole, and no toxicities have occurred that limited the dosage and no serious or unexpected side effects occurred. However, vincristine has never been given with fenretinide or fenretinide plus ketoconazole before. Vincristine has been been given before with ketoconazole to both children and adults with neuroblastomas and other cancers.
Detailed description
Fenretinide has been given by mouth as a capsule to many people, including children. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. This means patients have to take many capsules of fenretinide by mouth several times a day. In this study, a new oral preparation of fenretinide (called 4-HPR/LXS oral powder) is being tested to see if more fenretinide can be absorbed into the body. 4-HPR/LXS oral powder has been tested previously in a limited number of both children and adult cancer patients.
Ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. Ketoconazole will be given at the same time as the fenretinide powder.
There is preclinical data that shows that combining fenretinide and vincristine prolonged survival in animal models, therefore, it is hoped that giving the vincristine with fenretinide will work better against the neuroblastoma that either drug given alone.
About 70 children with neuroblastoma have been treated with various versions of the fenretinide powder to date, including about a dozen children that also took the fenretinide powder with ketoconazole, and no toxicities have occurred that limited the dosage and no serious or unexpected side effects occurred. However, vincristine has never been given with fenretinide or fenretinide plus ketoconazole before. Vincristine has been been given before with ketoconazole to both children and adults with neuroblastomas and other cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primary therapy | Experimental | Drug: Fenretinide/LXS Oral Powder, Drug: Ketoconazole, Drug: VincristineFenretinide/LXS oral powder 1500 mg/m2/day for 7 days plus ketoconazole 6 mg/kg/day for 7 days plus single dose vincristine (dose escalating) given on day 3. Starting dose of vincristine is 0.75 mg/m2/dose. Followed by 14 days of rest. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (40 listed)
- Diagnosed with neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
- Patients must have high-risk neuroblastoma with at least ONE of the following:
- Patients must have at least ONE of the following sites of disease:
- Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
- Patients must have a performance status of 0, 1 or 2 (Appendix I). Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Key exclusion criteria (13 listed)
- Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
- Pregnancy or breast feeding. Due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible. Breast milk feeding by study patient is NOT allowed
- Patients with history of organ and allogeneic stem cell transplantation
- Patients with a known history of allergy to soy products
- Patients with a known history of a severe allergy or sensitivity to wheat gluten
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 |
|---|---|---|
| Fenretinide/LXS Oral PowderAlso: 4-HPR, Fenretinide/Lym-X-Sorb, 4-HPR/LXSOral Powder | Drug | Primary therapy |
| KetoconazoleAlso: NizoralOral Tablet | Drug | Primary therapy |
| VincristineAlso: Oncovin, Vincristine SulfateIV | Drug | Primary therapy |
Primary outcome
Maximum Tolerated Dose
Time frame: after each subject has completed 1 cycle of therapy (a cycle is 21 days)
To determine maximum dose of vincristine when given in combination with 4-HPR/LXS and ketoconazole. Subjects will be enrolled in a standard 3 + 3 design and will receive set doses of HPR/LXS and ketoconazole. Vincristine will be escalated with each dose level up to 1.5 mg/m2. If toxicity occurs due to vincristine, the dose level will be expanded or dose decreased to the previous level as appropriate. If toxicity occurs due to ketoconazole, the dose level will be expanded and the ketoconazole dose decreased to 3 mg/kg/day
Side effect profile of drug combination
Time frame: after each subject receives the drug combination (a cycle is expected to be 21 days)
The side effect profile of the combination therapy will be compared to known single agent side effects looking for new unique drug interactions.
Assess plasma pharmacokinetics of fenretinide
Time frame: On day 1 (hour 0, 2, 4, 6), day 7 (hour 0, 2, 4, 6) and day 9 (after 3 pm) for course 1. For courses 2 and 6, day 1 (hour 0, 4 and 6), and day 7 (hour 0, 4, and 6)
included analysis of metabolites (4-MPR and 4-oxo-HPR) and related plasma sphingolipids
1 secondary outcome
Disease response
Time frame: every 42 days while on therapy
Results and safety
The study was stopped early (reason given: drug supply). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Individual participant dataSharing planned: Undecided
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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.
Tanya Watt, MD study chair
University of Texas Southwestern Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fenretinide/LXS Oral Powder, Ketoconazole and Vincristine in people with Recurrent Neuroblastoma and Neuroblastoma, run by South Plains Oncology Consortium at 4 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 40 inclusion and 13 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 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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 was stopped early (reason given: drug supply). Results are not available in the source record.
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 (time frame: after each subject has completed 1 cycle of therapy (a cycle is 21 days)). 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 31 Mar 2022.