NeuroblastomaPhase 1NCT00644696
Study of Irinotecan and Bortezomib in Children With Recurrent/Refractory Neuroblastoma
A Phase 1 study testing Irinotecan and Bortezomib in people with Neuroblastoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This Phase One pediatric trial seeks to take advantage of the susceptibility of neuroblastoma to proteasome inhibitors, proven in vitro, along with the proven in vitro synergy of bortezomib with irinotecan and the successful Phase One pediatric trials of bortezomib to create a treatment using these two drugs in… Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Irinotecan and Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Jul 2012
- 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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- No greater than 25 years of age when originally diagnosed.
- Histologic verification of condition.
- Has recurrent/progressive; or resistant/refractory neuroblastoma with at least ONE of the following:
- Measurable tumor on MRI or CT scan or X-ray (at least 20 mm in at least one dimension) or
- MIBG scan with positive uptake at minimum of one site, or
- Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy on one bone marrow sample.
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- Has Lansky or Karnofsky score of 60%, and a life expectancy of > 2 months.
- Has fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
- Has not received treatment with myelosuppressive agents within 3 weeks and with any biological therapy within 2 weeks of study entry.
- Has not received radiation for a minimum of four weeks prior to study entry at the site of any lesion that was biopsied to document study eligibility.
- Patient is 2 months post myeloablative therapy and autologous stem cell transplant.
- At least six weeks must have elapsed since treatment with therapeutic doses of MIBG.
- Patients who have previously received combination bortezomib and irinotecan are ineligible but can have received one of the drugs.
- Must not have received hematopoietic growth factors within 2 days of study entry.
- Cannot be receiving enzyme-inducing anticonvulsants (phenobarbital, phenytoin, carbamazepine).
- Concomitant radiotherapy to painful bone lesions will be allowed (excluding intestinal tract, spine or pelvis) but other non-radiated sites of measurable disease must be available to assess response to chemotherapy.
- Patient has adequate bone marrow function (defined).
- Patient has adequate renal function (defined).
- Patient has adequate liver function (defined).
- Post-menarchal females must have a negative pregnancy test measuring beta-human chorionic gonadotropin(HCG). All males and females must use effective contraception during study.
Who cannot join
- Patient is status post-allogenic stem cell transplant.
- Patient has uncontrolled infection or active diarrhea defined as 2 or more stools per day greater than baseline.
- Presence of HIV, active hepatitis B, or active hepatitis C infection.
- Pregnancy, as determined by Beta-human chorionic gonadotropin(HCG)measurement.
- Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or various other indications of heart disease. (defined)
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- Hypersensitivity to bortezomib, irinotecan, cefixime, boron or mannitol.
- Female subject is breast-feeding.
- Serious medical or psychiatric illness likely to interfere with participation.
- Patient has received other investigational drugs within 14 days before enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase One Study of Intravenous Irinotecan and Bortezomib in Children With Recurrent/Refractory High-Risk Neuroblastoma
This Phase One pediatric trial seeks to take advantage of the susceptibility of neuroblastoma to proteasome inhibitors, proven in vitro, along with the proven in vitro synergy of bortezomib with irinotecan and the successful Phase One pediatric trials of bortezomib to create a treatment using these two drugs in combination to treat refractory/recurrent neuroblastoma in children and young adults 25 and under.
Read the detailed description
In spite of intensive treatment including high-dose chemotherapy with autologous peripheral stem cell transplantation and radiation therapy, the long-term survival of patients with high-risk neuroblastoma remains poor. Patients who experience a relapse of their disease or fail to achieve complete remission fare even worse. More intense chemotherapy is not the answer. The development of new drugs with different mechanisms of action are required.
Inhibitors of the proteasome have created a considerable interest in their use in cancer chemotherapy, either as a single agent or in combination with other chemotherapeutic agents. The precise mechanism of action for these class of drugs is unclear, however, inhibition of I-kB degradation by VELCADE® (bortezomib) decreases NF-kB activity in neuroblastoma cell lines as well as other systems.
Previous studies have reported the activity of Irinotecan, a strong Topoisomerase-I inhibitor, against murine xenografts including those with high-risk features such as MYCN gene amplification (MYCN is also called V-Myc Myelocytomatosis Viral Related Oncogene, Neuroblastoma Derived). Irinotecan has also been shown to be active against neuroblastoma xenografts resistant to vincristine, melphalan, and topotecan, suggesting an alternative mechanism of resistance to Irinotecan. In vitro synergy between bortezomib and irinotecan has been documented in pancreatic cancer by others and in neuroblastoma by our group.
- Conditions
- Neuroblastoma
- Being tested
- Irinotecan and Bortezomib
- Keywords
- Neuroblastoma, Irinotecan, Bortezomib
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan and BortezomibDrug
Also called Velcade, Cefpodoxime, Cefixime
Dose level-1a: IV Irinotecan 30 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-1: IV Irinotecan 35 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-2: IV Irinotecan 40 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-3: IV Irinotecan 45 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-4: IV Irinotecan 50 mg/m2/day, IV bortezomib 1.2mg/m2/day
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan and Bortezomib | Experimental | Irinotecan and Bortezomib will both be administered Receives: Drug: Irinotecan and Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine highest dose of IV irinotecan administered in conjunction with bortezomib without causing severe side effects.
Measured: 3 years
Secondary outcomes (1)
Measure the neuroblastoma tumors after treatment with irinotecan and bortezomib to determine whether there was a change in size.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2008 (estimated)
- Study startApr 2008
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Rajen Mody, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00644696
- Sponsor's protocol ID
- UMCC 2006.084
- Other IDs
- HUM 7859
- Status last verified
- Jul 2017
- First submitted
- 24 Mar 2008
- Last updated
- 6 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase One Study of Intravenous Irinotecan and Bortezomib in Children With Recurrent/Refractory High-Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT00644696
- Acronym / sponsor ID
- UMCC 2006.084
- Conditions
- Neuroblastoma
- Keywords
- Neuroblastoma, Irinotecan, Bortezomib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Apr 2008
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 27 Mar 2008 (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 One pediatric trial seeks to take advantage of the susceptibility of neuroblastoma to proteasome inhibitors, proven in vitro, along with the proven in vitro synergy of bortezomib with irinotecan and the successful Phase One pediatric trials of bortezomib to create a treatment using these two drugs in combination to treat refractory/recurrent neuroblastoma in children and young adults 25 and under.
Detailed description
In spite of intensive treatment including high-dose chemotherapy with autologous peripheral stem cell transplantation and radiation therapy, the long-term survival of patients with high-risk neuroblastoma remains poor. Patients who experience a relapse of their disease or fail to achieve complete remission fare even worse. More intense chemotherapy is not the answer. The development of new drugs with different mechanisms of action are required.
Inhibitors of the proteasome have created a considerable interest in their use in cancer chemotherapy, either as a single agent or in combination with other chemotherapeutic agents. The precise mechanism of action for these class of drugs is unclear, however, inhibition of I-kB degradation by VELCADE® (bortezomib) decreases NF-kB activity in neuroblastoma cell lines as well as other systems.
Previous studies have reported the activity of Irinotecan, a strong Topoisomerase-I inhibitor, against murine xenografts including those with high-risk features such as MYCN gene amplification (MYCN is also called V-Myc Myelocytomatosis Viral Related Oncogene, Neuroblastoma Derived). Irinotecan has also been shown to be active against neuroblastoma xenografts resistant to vincristine, melphalan, and topotecan, suggesting an alternative mechanism of resistance to Irinotecan. In vitro synergy between bortezomib and irinotecan has been documented in pancreatic cancer by others and in neuroblastoma by our group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irinotecan and Bortezomib | Experimental | Drug: Irinotecan and BortezomibIrinotecan and Bortezomib will both be administered |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- No greater than 25 years of age when originally diagnosed.
- Histologic verification of condition.
- Has recurrent/progressive; or resistant/refractory neuroblastoma with at least ONE of the following:
- Has Lansky or Karnofsky score of 60%, and a life expectancy of > 2 months.
- Has fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
Key exclusion criteria (10 listed)
- Patient is status post-allogenic stem cell transplant.
- Patient has uncontrolled infection or active diarrhea defined as 2 or more stools per day greater than baseline.
- Presence of HIV, active hepatitis B, or active hepatitis C infection.
- Pregnancy, as determined by Beta-human chorionic gonadotropin(HCG)measurement.
- Grade 2 peripheral neuropathy within 14 days before enrollment.
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 |
|---|---|---|
| Irinotecan and BortezomibAlso: Velcade, Cefpodoxime, CefiximeDose level-1a: IV Irinotecan 30 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-1: IV Irinotecan 35 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-2: IV Irinotecan 40 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-3: IV Irinotecan 45 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-4: IV Irinotecan 50 mg/m2/day, IV bortezomib 1.2mg/m2/day | Drug | Irinotecan and Bortezomib |
Primary outcome
Determine highest dose of IV irinotecan administered in conjunction with bortezomib without causing severe side effects.
Time frame: 3 years
1 secondary outcome
Measure the neuroblastoma tumors after treatment with irinotecan and bortezomib to determine whether there was a change in size.
Time frame: 24 months
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 6 Jul 2017.
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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.
Rajen Mody, MD principal investigator
University of Michigan Rogel 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 Irinotecan and Bortezomib in people with Neuroblastoma, run by University of Michigan Rogel Cancer Center 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 20 inclusion and 10 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 6 Jul 2017. 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?
Determine highest dose of IV irinotecan administered in conjunction with bortezomib without causing severe side effects. (time frame: 3 years). 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 Jul 2017.