Adrenocortical CarcinomaPhase 1NCT01048892
Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
A Phase 1 study testing Seneca Valley virus-001, cyclophosphamide and laboratory biomarker analysis in people with Adrenocortical Carcinoma and Gastrointestinal Carcinoid Tumor, run by Children's Oncology Group at 18 sites in United States.
Trial summary
RATIONALE: Seneca Valley virus-001 may be able to kill certain kinds of tumor cells without damaging normal cells. Adding low dose cyclophosphamide (in part B of study) may help to kill even more tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Adrenocortical Carcinoma, Gastrointestinal Carcinoid Tumor, Kidney Cancer
- What is being tested?
- Seneca Valley virus-001, cyclophosphamide and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 18 sitesUnited States
- Study dates
- Sep 2009to Jun 2013
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Neuroblastoma
- Rhabdomyosarcoma
- Wilms tumor
- Retinoblastoma
- Adrenocortical carcinoma
- Carcinoid tumor
- Relapsed or refractory disease
- Measurable or evaluable disease
- No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- No known pulmonary tumors or metastases > 5 cm, as evaluated by chest CT scan
- No clinically significant pulmonary and/or pericardial effusions (≥ grade 3), as evaluated by ECHO
- No primary CNS tumors or known metastatic CNS disease involvement
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age)
- Lansky PS 50-100% (for patients ≤ 16 years of age)
- Peripheral ANC ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent, defined as no platelet transfusions within a 7-day period before study enrollment)
- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
- Creatine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- ≤ 0.8 mg/dL (for patients 3 to 5 years of age)
- ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
- ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
- ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
- ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
- Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal (ULN)
- SGPT ≤ 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
- Serum albumin ≥ 2 g/dL
- Oxygen saturation > 92% on room air
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to comply with the safety monitoring requirements of the study, in the opinion of the investigator
- Completely toilet trained
- No chronic diarrhea or urinary incontinence during the day or night, , and no in-dwellling urinary catheters
- No uncontrolled infection
- No known pregnant member of the household
PRIOR CONCURRENT THERAPY:
- Fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
- At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
- At least 3 months since prior stem cell transplantation or rescue (without TBI)
- No evidence of active graft-vs-host disease
- At least 6 weeks since other prior substantial bone marrow radiotherapy or treatment with therapeutic doses of MIBG
- More than 3 weeks since prior myelosuppressive chemotherapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- More than 7 days since prior growth factor(s) that support platelet or white blood cell number or function
- At least 7 days since prior biologic agents
- At least 3 half-lives since prior monoclonal antibodies
- More than 7 days since prior viral immunizations, including influenza
- At least 42 days since the completion of any type of immunotherapy, e.g., tumor vaccines
- No other viral immunizations after enrolling on study until 28 days after their last planned Seneca Valley virus-001 infusion or until documented viral clearance, whichever is longest
- Concurrent corticosteroids allowed provided the patient has been on a stable or decreasing dose for the past 7 days
- No other concurrent investigational drugs
- No other concurrent anticancer agents (e.g., chemotherapy, radiotherapy, immunotherapy, or biologic therapy)
- Prior treatment with Seneca Valley virus-001 is not allowed
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, 48109-0286
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, 2115
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
Baylor University Medical Center - Houston
Houston, Texas, 77030-2399
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, 46202
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15213
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
Official title: A Phase 1 Dose Escalation Study of Seneca Valley Virus (NTX-010), A Replication-Competent Picornavirus, in Relapsed/Refractory Pediatric Patients With Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
RATIONALE: Seneca Valley virus-001 may be able to kill certain kinds of tumor cells without damaging normal cells. Adding low dose cyclophosphamide (in part B of study) may help to kill even more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of Seneca Valley virus-001 in treating young patients with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features.
Read the detailed description
OBJECTIVES:
Primary
- To estimate the maximum-tolerated dose and/or recommended phase II dose of Seneca Valley virus-001 (NTX-010) when administered as a single infusion to pediatric patients with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features (Wilms tumor, retinoblastoma, adrenocortical carcinoma, or carcinoid tumors). (Part A [completed])
- To confirm that there is viral replication in these patients following NTX-010 administration. (Part A [completed])
- To define and describe the toxicities of NTX-010 when administered on this schedule. (Part A [completed])
- To determine whether the number of regulatory T cells (as measured by flow cytometry) can effectively be reduced following administration of NTX-010 plus low-dose metronomic and intravenous cyclophosphamide. (Part B)
- To characterize the pharmacokinetics (time course of viral clearance) following NTX-010 administration in these patients.
Secondary
- To preliminarily define the antitumor activity of NTX-010 within the confines of a phase I study. (Part A [completed])
- To evaluate the development of neutralizing antibodies to NTX-010 following IV administration of NTX-010. (Part A [completed])
- To evaluate development of neutralizing antibodies to NTX-010 following the combination of NTX-010 and cyclophosphamide. (Part B)
- To investigate the presence and permissivity of occult circulating tumor cells prior to and after the initial intravenous administration of NTX-010.
OUTLINE: This is a multicenter study.
Part A (completed): Patients receive Seneca Valley virus-001 (NTX-010) IV over 1 hour on day 1.
Part B: Patients receive cyclophosphamide IV orally (PO) on days 1-14 and NTX-010 IV over 1 hour on day 8. In the absence of disease progression or unacceptable toxicity, patients then receive cyclophosphamide orally (PO) on days 22-35, plus cyclophosphamide IV over 1 hour and NTX-010 IV over 1 hour on day 29.
Tumor tissue samples are collected at baseline for biomarker studies. Blood and stool samples are collected periodically for neutralizing antibody and viral clearance studies. Additional blood samples may also be collected for the presence and permissivity of occult tumor cells.
After completion of study treatment, patients are followed up periodically for up to 1 year.
- Conditions
- Adrenocortical Carcinoma, Gastrointestinal Carcinoid Tumor, Kidney Cancer, Neuroblastoma, Retinoblastoma, Sarcoma
- Being tested
- Seneca Valley virus-001, cyclophosphamide, laboratory biomarker analysis, pharmacological study
- Keywords
- recurrent neuroblastoma, previously treated childhood rhabdomyosarcoma, recurrent childhood rhabdomyosarcoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent retinoblastoma, recurrent adrenocortical carcinoma, recurrent gastrointestinal carcinoid tumor
- Medical subject headings
- Adrenocortical Carcinoma, Kidney Neoplasms, Neuroblastoma, Retinoblastoma, Sarcoma, Wilms Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seneca Valley virus-001Biological
cyclophosphamideDrug
laboratory biomarker analysisOther
| Study group | Role | What they receive |
|---|---|---|
| Treatment (NTX-010) | Experimental | Not described Receives: Biological: Seneca Valley virus-001; Drug: cyclophosphamide; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Measured: 12 months post-documented viral clearance
Recommended phase II dose of Seneca Valley virus-001 (NTX-010)
Measured: 56 days
Secondary outcomes (3)
Tumor response
Measured: Up to 12 months post documented viral clearance
Viral titers in blood and stool
Measured: Up to 56 days post treatment
Development of antibodies to NTX-010
Measured: Up to 4 weeks post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2010 (estimated)
- Study startSep 2009
- Primary completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adrenocortical CarcinomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael J. Burke, MD, Study chair, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01048892
- Sponsor's protocol ID
- ADVL0911
- Other IDs
- COG-ADVL0911, CDR0000663520
- Status last verified
- Jan 2014
- First submitted
- 13 Jan 2010
- Last updated
- 30 Jan 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of Seneca Valley Virus (NTX-010), A Replication-Competent Picornavirus, in Relapsed/Refractory Pediatric Patients With Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
- ClinicalTrials.gov ID
- NCT01048892
- Acronym / sponsor ID
- ADVL0911
- Conditions
- Adrenocortical Carcinoma, Gastrointestinal Carcinoid Tumor, Kidney Cancer, Neuroblastoma, Retinoblastoma, Sarcoma
- Keywords
- recurrent neuroblastoma, previously treated childhood rhabdomyosarcoma, recurrent childhood rhabdomyosarcoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent retinoblastoma, recurrent adrenocortical carcinoma, recurrent gastrointestinal carcinoid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2009
- Primary completion
- Jun 2013 (actual)
- First posted
- 14 Jan 2010 (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.
RATIONALE: Seneca Valley virus-001 may be able to kill certain kinds of tumor cells without damaging normal cells. Adding low dose cyclophosphamide (in part B of study) may help to kill even more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of Seneca Valley virus-001 in treating young patients with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features.
Detailed description
OBJECTIVES:
Primary
- To estimate the maximum-tolerated dose and/or recommended phase II dose of Seneca Valley virus-001 (NTX-010) when administered as a single infusion to pediatric patients with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features (Wilms tumor, retinoblastoma, adrenocortical carcinoma, or carcinoid tumors). (Part A [completed])
- To confirm that there is viral replication in these patients following NTX-010 administration. (Part A [completed])
- To define and describe the toxicities of NTX-010 when administered on this schedule. (Part A [completed])
- To determine whether the number of regulatory T cells (as measured by flow cytometry) can effectively be reduced following administration of NTX-010 plus low-dose metronomic and intravenous cyclophosphamide. (Part B)
- To characterize the pharmacokinetics (time course of viral clearance) following NTX-010 administration in these patients.
Secondary
- To preliminarily define the antitumor activity of NTX-010 within the confines of a phase I study. (Part A [completed])
- To evaluate the development of neutralizing antibodies to NTX-010 following IV administration of NTX-010. (Part A [completed])
- To evaluate development of neutralizing antibodies to NTX-010 following the combination of NTX-010 and cyclophosphamide. (Part B)
- To investigate the presence and permissivity of occult circulating tumor cells prior to and after the initial intravenous administration of NTX-010.
OUTLINE: This is a multicenter study.
Part A (completed): Patients receive Seneca Valley virus-001 (NTX-010) IV over 1 hour on day 1.
Part B: Patients receive cyclophosphamide IV orally (PO) on days 1-14 and NTX-010 IV over 1 hour on day 8. In the absence of disease progression or unacceptable toxicity, patients then receive cyclophosphamide orally (PO) on days 22-35, plus cyclophosphamide IV over 1 hour and NTX-010 IV over 1 hour on day 29.
Tumor tissue samples are collected at baseline for biomarker studies. Blood and stool samples are collected periodically for neutralizing antibody and viral clearance studies. Additional blood samples may also be collected for the presence and permissivity of occult tumor cells.
After completion of study treatment, patients are followed up periodically for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (NTX-010) | Experimental | Biological: Seneca Valley virus-001, Drug: cyclophosphamide, Other: laboratory biomarker analysis, Other: pharmacological study |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| Seneca Valley virus-001 | Biological | Treatment (NTX-010) |
| cyclophosphamide | Drug | Treatment (NTX-010) |
| laboratory biomarker analysis | Other | Treatment (NTX-010) |
| pharmacological study | Other | Treatment (NTX-010) |
Primary outcome
Safety and tolerability
Time frame: 12 months post-documented viral clearance
Recommended phase II dose of Seneca Valley virus-001 (NTX-010)
Time frame: 56 days
3 secondary outcomes
Tumor response
Time frame: Up to 12 months post documented viral clearance
Viral titers in blood and stool
Time frame: Up to 56 days post treatment
Development of antibodies to NTX-010
Time frame: Up to 4 weeks post treatment
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 30 Jan 2014.
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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.
Michael J. Burke, MD study chair
Masonic Cancer Center, University of Minnesota
18 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 Seneca Valley virus-001, cyclophosphamide and laboratory biomarker analysis in people with Adrenocortical Carcinoma and Gastrointestinal Carcinoid Tumor, run by Children's Oncology Group at 18 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?
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 30 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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 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?
Safety and tolerability (time frame: 12 months post-documented viral clearance). 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 30 Jan 2014.