Clinical trial NCT01048892: Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-01-14
Enrollment: 22
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability
timeFrame: 12 months post-documented viral clearance
measure: Recommended phase II dose of Seneca Valley virus-001 (NTX-010)
timeFrame: 56 days
Secondary outcomes:
measure: Tumor response
timeFrame: Up to 12 months post documented viral clearance
measure: Viral titers in blood and stool
timeFrame: Up to 56 days post treatment
measure: Development of antibodies to NTX-010
timeFrame: Up to 4 weeks post treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley's Children Cancer Center at Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center at Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Michael J. Burke, MD
role: STUDY_CHAIR
References: