Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048892
• Other study ID #: ADVL0911
• Secondary ID: COG-ADVL0911CDR0
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2010
• Last updated: January 29, 2014
• Start date: September 2009

Study information

• Verified date: January 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Carcinoid Tumor
• Gastrointestinal Carcinoid Tumor
• Gastrointestinal Neoplasms
• Kidney Cancer
• Malignant Carcinoid Syndrome
• Neuroblastoma
• Neuroendocrine Tumors
• Retinoblastoma
• Rhabdomyosarcoma
• Sarcoma

Intervention

Biological:
• Seneca Valley virus-001

Drug:
• cyclophosphamide

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Riley's Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center at Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St. Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability		12 months post-documented viral clearance	Yes
Primary	Recommended phase II dose of Seneca Valley virus-001 (NTX-010)		56 days	No
Secondary	Tumor response		Up to 12 months post documented viral clearance	No
Secondary	Viral titers in blood and stool		Up to 56 days post treatment	No
Secondary	Development of antibodies to NTX-010		Up to 4 weeks post treatment	No