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

Children's Oncology Group

Status and phase

Completed

Phase 1

Conditions

Sarcoma

Neuroblastoma

Gastrointestinal Carcinoid Tumor

Adrenocortical Carcinoma

Kidney Cancer

Retinoblastoma

Treatments

Drug: cyclophosphamide

Other: pharmacological study

Other: laboratory biomarker analysis

Biological: Seneca Valley virus-001

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT01048892

ADVL0911

COG-ADVL0911

CDR0000663520 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

22 patients

Sex

All

Ages

3 to 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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