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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
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

Other trials in United States

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.

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.

Study groups in NCT01048892
Study groupRoleWhat they receive
Treatment (NTX-010)ExperimentalNot 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.

  1. Safety and tolerability

    Measured: 12 months post-documented viral clearance

  2. Recommended phase II dose of Seneca Valley virus-001 (NTX-010)

    Measured: 56 days

Secondary outcomes (3)
  1. Tumor response

    Measured: Up to 12 months post documented viral clearance

  2. Viral titers in blood and stool

    Measured: Up to 56 days post treatment

  3. 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.

  1. First posted14 Jan 2010 (estimated)
  2. Study startSep 2009
  3. Primary completionJun 2013

Resources

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)
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

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.

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