A Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors
| Status: | Recruiting |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 18 |
| Updated: | 2/24/2018 |
| Start Date: | June 2016 |
| End Date: | June 2019 |
| Contact: | Sarah Whittle, MD, BA |
| Email: | sbwhittl@txch.org |
| Phone: | 832-822-4242 |
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.
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.
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.
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.
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.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
We found this trial at
2
sites
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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San Diego, California 92123
Principal Investigator: Peter Zage, MD
Phone: 858-966-5983
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