NeuroblastomaSPRINGNCT02786719
High-Risk Neuroblastoma Chemotherapy Without G-CSF
A study testing Topotecan, Cyclophosphamide and Cisplatin in people with Neuroblastoma, run by Baylor College of Medicine at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 18 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Topotecan, Cyclophosphamide and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2016to 5 Feb 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- Patients who do not meet inclusion criteria
- Patients who are pregnant or lactating
- Patients who have received G-CSF since the time of diagnosis of the current disease
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
Rady Children's Hospital
San Diego, California, 92123
About this study
Official title: A Safety Pilot Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors
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.
Read more
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.
Read the detailed description
Chemotherapy:
CYCLE 1+2: Topotecan and cyclophosphamide
Cycle 3+5: Cisplatin and Etoposide
Cycle 4+6: Vincristine, Cyclophosphamide and Doxorubicin
Stem cell collection: After the third cycle of chemotherapy, stem cells will be collected for possible stem cell transplantation at a later date using apheresis. In order to have enough stem cells present in the blood, the patient will need to receive daily G-CSF injections before this collection.
Surgery: After the 5th cycle of chemotherapy, most patients will have surgery to remove as much remaining tumor as possible.
Growth factor support: Growth factors to increase the number of white blood cells, G-CSF and GM-CSF(granulocyte-macrophage colony stimulating factor) will not be given routinely in this study. GM-CSF will be given for patients who have serious bacterial infections or delays in administering chemotherapy because of low neutrophil counts. All people enrolled on the study will receive GM-CSF prior to having surgical removal of the main tumor. All people enrolled on the study will also receive G-CSF prior to having patients stem cells collected.
Optional survey: This research study includes an optional survey regarding quality of life while on the study. This survey will be filled out after cycles 1 and 4 of chemotherapy.
Drug Shortages:
In the event of a drug shortage of a medication that is not a G-CSF or GM-CSF product, the provider may use best clinical judgment regarding omission of the agent or substitution with a different agent. The medical and research records of study patients should reflect that the patient was informed of any delays and/or modifications in protocol therapy related to the shortage of the agent and the associated risks.
- Conditions
- Neuroblastoma
- Being tested
- Topotecan, Cyclophosphamide, Cisplatin, Etoposide, Vincristine
- Keywords
- Sargramostim, Cyclophosphamide, Topotecan, Cisplatin, Dexrazoxane, Doxorubicin, Etoposide, Filgrastim, Vincristine, Mesna
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
Also called hycamtin
CYCLE 1+2 (given by intravenous catheter daily for 5 days)
CyclophosphamideDrug
Also called Cytoxan
CYCLE 1+2 (given by intravenous catheter daily for 5 days)
CisplatinDrug
Also called CDDP, Platinol
Cycle 3+5 (given daily x 4 days)
EtoposideDrug
Cycle 3+5 (given daily for 3 days)
VincristineDrug
Also called Oncovin
Cycle 4+6 (given daily for 3 days)
CyclophosphamideDrug
Also called Cytoxan
Cycle 4+6 (given daily for 2 days)
DoxorubicinDrug
Also called Adriamycin
Cycle 4+6 (given daily for 3 days)
SargramostimDrug
Also called GM-CSF
Granulocyte macrophage colony stimulating factor (rhu GM-CSF, rGM-CSF, GM-CSF)
| Study group | Role | What they receive |
|---|---|---|
| Neuroblastoma treatment without G-CSF | Experimental | Induction chemotherapy only, including 6 cycles of chemotherapy, tumor resection, and stem cell collection Receives: Drug: Topotecan; Drug: Cyclophosphamide; Drug: Cisplatin; Drug: Etoposide; Drug: Vincristine; Drug: Doxorubicin; Drug: Sargramostim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Infection
Incidence of infections in chemotherapy cycles NOT followed by hematopoietic growth factors
Measured: through study completion, approximately 5 months
Secondary outcomes (2)
Delay in Chemotherapy Administration Due to Prolonged Neutrophil Recovery
incidence of delay in chemotherapy administration due to prolonged neutrophil recovery
Measured: through study completion, approximately 5 months
the Response Rate Following Induction Chemotherapy Without Prophylactic Granulocyte Colony Stimulating Factor (G-CSF)
Response rate in the participants that completed all 6 cycles of induction chemotherapy on study. Response rate as categorize by International neuroblastoma response criteria.
- Complete response (CR): No evidence of primary tumor; no evidence of metastases (chest, abdomen, liver, bone, bone marrow, nodes, etc.), and urine catecholamines homovanillic acid (HVA)/ vanillylmandelic acid (VMA) normal. MIBG scan must be negative to qualify for CR.
- Very good partial response (VGPR): Greater than 90% reduction in primary tumor; no metastatic tumor (as above except bone); no new bone lesions, all pre-existing lesions improved, HVA/VMA normal
- Partial Response (PR): 50-90% reduction of primary tumor; 50% or greater reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by 50%
Measured: through study completion, approximately 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion5 Feb 2019
- Study completion5 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sarah Whittle, Baylor College of Medicine
- Investigators
- Sarah Whittle, MD, BA, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02786719
- Sponsor's protocol ID
- H-38179 (SPRING)
- Other IDs
- SPRING
- Acronym
- SPRING
- Status last verified
- Mar 2020
- First submitted
- 23 May 2016
- Last updated
- 12 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety Pilot Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors
- ClinicalTrials.gov ID
- NCT02786719
- Acronym / sponsor ID
- SPRING / H-38179 (SPRING)
- Conditions
- Neuroblastoma
- Keywords
- Sargramostim, Cyclophosphamide, Topotecan, Cisplatin, Dexrazoxane, Doxorubicin, Etoposide, Filgrastim
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- 5 Feb 2019 (actual)
- Study completion
- 5 Feb 2019 (actual)
- First posted
- 1 Jun 2016 (estimated)
- Results
- Posted 12 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Chemotherapy:
CYCLE 1+2: Topotecan and cyclophosphamide
Cycle 3+5: Cisplatin and Etoposide
Cycle 4+6: Vincristine, Cyclophosphamide and Doxorubicin
Stem cell collection: After the third cycle of chemotherapy, stem cells will be collected for possible stem cell transplantation at a later date using apheresis. In order to have enough stem cells present in the blood, the patient will need to receive daily G-CSF injections before this collection.
Surgery: After the 5th cycle of chemotherapy, most patients will have surgery to remove as much remaining tumor as possible.
Growth factor support: Growth factors to increase the number of white blood cells, G-CSF and GM-CSF(granulocyte-macrophage colony stimulating factor) will not be given routinely in this study. GM-CSF will be given for patients who have serious bacterial infections or delays in administering chemotherapy because of low neutrophil counts. All people enrolled on the study will receive GM-CSF prior to having surgical removal of the main tumor. All people enrolled on the study will also receive G-CSF prior to having patients stem cells collected.
Optional survey: This research study includes an optional survey regarding quality of life while on the study. This survey will be filled out after cycles 1 and 4 of chemotherapy.
Drug Shortages:
In the event of a drug shortage of a medication that is not a G-CSF or GM-CSF product, the provider may use best clinical judgment regarding omission of the agent or substitution with a different agent. The medical and research records of study patients should reflect that the patient was informed of any delays and/or modifications in protocol therapy related to the shortage of the agent and the associated risks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neuroblastoma treatment without G-CSF | Experimental | Drug: Topotecan, Drug: Cyclophosphamide, Drug: Cisplatin, Drug: Etoposide, Drug: Vincristine, Drug: Doxorubicin, Drug: SargramostimInduction chemotherapy only, including 6 cycles of chemotherapy, tumor resection, and stem cell collection |
Who may qualify
- Ages
- 12 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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 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.
Key exclusion criteria (3 listed)
- Patients who do not meet inclusion criteria
- Patients who are pregnant or lactating
- Patients who have received G-CSF since the time of diagnosis of the current disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopotecanAlso: hycamtinCYCLE 1+2 (given by intravenous catheter daily for 5 days) | Drug | Neuroblastoma treatment without G-CSF |
| CyclophosphamideAlso: CytoxanCYCLE 1+2 (given by intravenous catheter daily for 5 days) | Drug | Neuroblastoma treatment without G-CSF |
| CisplatinAlso: CDDP, PlatinolCycle 3+5 (given daily x 4 days) | Drug | Neuroblastoma treatment without G-CSF |
| EtoposideCycle 3+5 (given daily for 3 days) | Drug | Neuroblastoma treatment without G-CSF |
| VincristineAlso: OncovinCycle 4+6 (given daily for 3 days) | Drug | Neuroblastoma treatment without G-CSF |
| CyclophosphamideAlso: CytoxanCycle 4+6 (given daily for 2 days) | Drug | Neuroblastoma treatment without G-CSF |
| DoxorubicinAlso: AdriamycinCycle 4+6 (given daily for 3 days) | Drug | Neuroblastoma treatment without G-CSF |
| SargramostimAlso: GM-CSFGranulocyte macrophage colony stimulating factor (rhu GM-CSF, rGM-CSF, GM-CSF) | Drug | Neuroblastoma treatment without G-CSF |
Primary outcome
Incidence of Infection
Time frame: through study completion, approximately 5 months
Incidence of infections in chemotherapy cycles NOT followed by hematopoietic growth factors
2 secondary outcomes
Delay in Chemotherapy Administration Due to Prolonged Neutrophil Recovery
Time frame: through study completion, approximately 5 months
the Response Rate Following Induction Chemotherapy Without Prophylactic Granulocyte Colony Stimulating Factor (G-CSF)
Time frame: through study completion, approximately 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Whittle, MD, BA principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Topotecan, Cyclophosphamide and Cisplatin in people with Neuroblastoma, run by Baylor College of Medicine at 2 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?
The sponsor lists 12 inclusion and 3 exclusion criteria. 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 12 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Incidence of Infection (time frame: through study completion, approximately 5 months). 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 12 Mar 2020.