High-Risk Neuroblastoma Chemotherapy Without G-CSF

NCT02786719 | Completed Results DMC

• 2 other identifiers: H-38179 (SPRING)SPRING
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

Patients will be asked to participate in this study because patients have been diagnosed with high-risk neuroblastoma, a common childhood cancer which has aggressive features. If left untreated, high-risk neuroblastoma is fatal. Children with high-risk neuroblastoma often respond to current available treatments, but there is a high risk that the cancer will return. This study will test the safety of giving standard induction treatment for high-risk neuroblastoma without one of the drugs commonly used to prevent side effects. Current treatment for high-risk neuroblastoma includes anti-cancer drugs (chemotherapy), surgery, radiation therapy and high-dose chemotherapy with hematopoietic stem cell rescue. Treatment takes about one year to complete and occurs in 3 phases: induction, consolidation, and maintenance. This study is limited to the induction phase of treatment. Induction therapy includes six chemotherapy drugs given in different combinations every 3 weeks for a total of 6 courses. For the past decade, induction chemotherapy has been followed by a drug called granulocyte colony stimulating factor (G-CSF, filgrastim, peg-filgrastim, Neupogen, or Neulasta) to prevent side effects from the chemotherapy. G-CSF is routinely given to patients with high risk neuroblastoma after chemotherapy to stimulate white blood cell production and shorten the time period when the absolute neutrophil count (ANC), a type of white blood cell, is low after chemotherapy. G-CSF is known to shorten the period of low ANC by approximately 3 days. When the ANC is lowest, a patient is most at risk of getting a bacterial infection. Recent lab experiments in mice have shown that neuroblastoma tumor cells may respond to G-CSF by growing faster and metastasizing (spreading to other parts of the body). There have been no clinical trials comparing the survival of children with high risk neuroblastoma with or without G-CSF. This clinical trial is the first step towards giving induction chemotherapy with less G-CSF. The goal of this study is to determine if it is safe to give induction chemotherapy to children with neuroblastoma without giving G-CSF routinely.

Conditions

Neuroblastoma

Keywords

Sargramostim; Cyclophosphamide; Topotecan; Cisplatin; Dexrazoxane; Doxorubicin; Etoposide; Filgrastim; Vincristine; Mesna

Outcome Measures

Primary Outcomes (1)

• Incidence of Infection

  Incidence of infections in chemotherapy cycles NOT followed by hematopoietic growth factors

  through study completion, approximately 5 months

Secondary Outcomes (2)

• Delay in Chemotherapy Administration Due to Prolonged Neutrophil Recovery

  through study completion, approximately 5 months

• the Response Rate Following Induction Chemotherapy Without Prophylactic Granulocyte Colony Stimulating Factor (G-CSF)

  through study completion, approximately 5 months

Study Arms (1)

Neuroblastoma treatment without G-CSF

EXPERIMENTAL

Induction chemotherapy only, including 6 cycles of chemotherapy, tumor resection, and stem cell collection

Drug: Topotecan; Drug: Cyclophosphamide; Drug: Cisplatin; Drug: Etoposide; Drug: Vincristine; Drug: Doxorubicin; Drug: Sargramostim

Interventions

Topotecan DRUG

CYCLE 1+2 (given by intravenous catheter daily for 5 days)

Also known as: hycamtin

Neuroblastoma treatment without G-CSF

Cyclophosphamide DRUG

CYCLE 1+2 (given by intravenous catheter daily for 5 days)

Also known as: Cytoxan

Neuroblastoma treatment without G-CSF

Cisplatin DRUG

Cycle 3+5 (given daily x 4 days)

Also known as: CDDP, Platinol

Neuroblastoma treatment without G-CSF

Etoposide DRUG

Cycle 3+5 (given daily for 3 days)

Neuroblastoma treatment without G-CSF

Vincristine DRUG

Cycle 4+6 (given daily for 3 days)

Also known as: Oncovin

Neuroblastoma treatment without G-CSF

Doxorubicin DRUG

Cycle 4+6 (given daily for 3 days)

Also known as: Adriamycin

Neuroblastoma treatment without G-CSF

Sargramostim DRUG

Granulocyte macrophage colony stimulating factor (rhu GM-CSF, rGM-CSF, GM-CSF)

Also known as: GM-CSF

Neuroblastoma treatment without G-CSF

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age greater than 12 months and less than 18 years old at diagnosis
• Newly diagnosed neuroblastoma or ganglioneuroblastoma as verified by histology and/or demonstration of tumor cells in bone marrow with elevated urinary catecholamine metabolites
• Must meet criteria for High Risk disease
• Patients with International Neuroblastoma Staging System (INSS) stage 4 disease are eligible with the following: MYCN gene amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features, Age greater than 18 months ( greater than 547 days) regardless of biologic features, Age 12 -18 months (365 - 547 days) with any of the following unfavorable biologic features (unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown
• Patients with INSS stage 3 disease are eligible with the following: MYCN amplification, regardless of age or additional biologic features, Age greater than 18 months ( greater than 547 days) with unfavorable pathology, regardless of MYCN status
• Patients with INSS stage 2a/2b with MYCN amplification regardless of age or additional biologic features
• Patients greater than or equal to 365 days initially diagnosed with INSS stage 1 or 2 who progressed to a stage 4 without interval chemotherapy
• Patients may have had no prior systemic therapy except: Localized emergency radiation to sites of life threatening or functioning disease, No more than 1 cycle of chemotherapy according to low or intermediate risk regimens prior to determination of MYCN amplification and histology, as long as the patient DID NOT receive any type of granulocyte colony stimulating factor (G-CSF) as part of that therapy.
• Patients must have adequate hematopoietic function defined as: Absolute neutrophil count (ANC) greater than or equal to 750/μL, Platelet count greater than or equal to 75,000/μL, The above criteria do not have to be met if the patient has bone marrow involvement of tumor.
• Patients must have adequate liver function defined as: Direct bilirubin less than or equal to 1.5 mg/dL or total bilirubin ≤ 1.5 mg/dL, aspartate aminotrasnferase (AST) and alanine aminotransferase (ALT) less than or equal to10 x upper limit of normal for age
• Patients must have adequate renal function as defined as: Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) greater than or equal to 70 mL/min/.73 m2 OR A serum creatinine based on age/gender.
• Patients must have adequate cardiac function as defined as: Shortening fraction of greater than or equal to 27 % by echocardiogram, or Ejection fraction of greater than or equal to 50 % by radionuclide angiogram

You may not qualify if:

• Patients who are pregnant or lactating
• Patients who have received G-CSF since the time of diagnosis of the current disease

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (2)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Topotecan; Cyclophosphamide; Cisplatin; Etoposide; Vincristine; Doxorubicin; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

This study was designed to pilot safely decreasing exposure to G-CSF. To formally test the non-inferiority of not giving G-CSF a much larger sample size would be needed. This study does not conclude that G-CSF prevents infections.

Results Point of Contact

• Title: Sarah Whittle, MD MS
• Organization: Baylor College of Medicine

whittle@bcm.edu

8328241471

Study Officials

• Sarah Whittle, MD, BA

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: June 1, 2016
• Study Start: June 1, 2016
• Primary Completion: February 5, 2019
• Study Completion: February 5, 2019
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2020-03

Locations

US (2)