NeuroblastomaPhase 2PEPINCT00578864
Protracted Etoposide During Induction Therapy for High Risk Neuroblastoma
A Phase 2 study testing Protracted Oral Etoposide, Doxorubicin and IV Bolus Etoposide in people with Neuroblastoma, run by Baylor College of Medicine at 1 site in United States.
Trial summary
High-risk neuroblastoma is an aggressive childhood cancer that shows up as a lump or mass in the belly or around the spinal cord in the chest, neck, or pelvis. Often the tumor has spread around the body to the bones or to the soft center of the bone, called the bone marrow. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Protracted Oral Etoposide, Doxorubicin and IV Bolus Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Mar 2015
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Pts can be enrolled but receive standard etoposide bolus dosing based on clinical conditions at diagnosis (need for emergency intervention because of renal, neurologic, or airway compromise). Pts who meet all other eligibility criteria may also choose to participate in the clinical trial w/o receiving the upfront window protracted dosing of etoposide; these children will receive standard etoposide bolus dosing.
- Less than 18 yo at diagnosis
- DIAGNOSIS Neuroblastoma or ganglioneuroblastoma verified by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
- Pts with newly diagnosed neuroblastoma and age 365 or more days with the following: INSS Stage 2a/2b with MYCN amplification , AND unfavorable pathology INSS Stage 3 with MYCN amplification AND/OR unfavorable pathology
- Pts with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following: Age more than 18 months (greater than 547 days) regardless of biologic features Age 12 to 18 months (365-547 days) with any unfavorable biologic feature (MYCN amplification, unfavorable pathology and/or DNA index equal to 1) or any biologic feature that is indeterminant/unsatisfactory/unknown.
- Pts with newly diagnosed neuroblastoma and age less than 365 days with INSS Stage 3, 4, 4S neuroblastoma with MYCN amplification (more than 10).
Show all 19Show fewer
- Pts 365 days or more initially diagnosed with INSS stage 1, 2, 4S who develop distant metastatic disease (meet criteria for INSS stage 4).
- Pts may have had no prior systemic therapy except:
- Localized emergency radiation to sites of life threatening or function-threatening disease
- No more than one cycle of chemotherapy according to the intergroup low or intermediate risk neuroblastoma studies prior to determination of MYCN amplification and histology.
- TIME FROM DIAGNOSIS Pts must be entered on this study - Within 3 weeks of diagnosis - After recovery from only 1 cycle of chemo on low/intermediate risk NB therapy, - Within 3 weeks of progression with widely metastatic tumor for INSS stage 1, 2, 4S if they received no prior chemotherapy.
- HEMATOPOIETIC FUNCTION
- ANC 750/µL or more
- Plt 75,000/µL or more
- or bone marrow involvement with tumor.
- LIVER FUNCTION Pts must have adequate liver function defined as
- Direct Bilirubin 1.5 mg/dL or less
- AST and ALT 5 x ULN or less
- Pts of childbearing potential must practice an effective method of birth control while on study.
Who cannot join
- Patients who do not meet inclusion criteria.
- Patients who are pregnant or lactating are not eligible.
- EXCLUSION CRITERIA UPFRONT WINDOW Patients can be enrolled onto Stratum 1 but receive standard etoposide bolus dosing based on clinical conditions at diagnosis. Patients who meet all other eligibility criteria may also choose to participate in the clinical trial without receiving the upfront window protracted dosing of etoposide; these children will receive standard etoposide bolus dosing.
- Patients whose tumor requires emergency intervention because of spinal cord compression, CNS compromise, or airway compromise.
- Patients requiring dialysis.
- If the patient and/or the patient's legally authorized guardian chose to participate in the clinical trial but chose to not participate in the phase II upfront window.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PEPI: Protracted Etoposide in a Phase II Upfront Window for Induction Therapy for High Risk Neuroblastoma
High-risk neuroblastoma is an aggressive childhood cancer that shows up as a lump or mass in the belly or around the spinal cord in the chest, neck, or pelvis. Often the tumor has spread around the body to the bones or to the soft center of the bone, called the bone marrow. High-risk neuroblastoma often responds to treatment at first, but it frequently comes back and may be even more difficult to treat.
Chemotherapy (drug treatments for cancer) is usually given at high doses in short bursts (3 to 5 days) followed by a few weeks of rest and recovery. This burst and recovery is called a "cycle" and usually takes about 21 days. Some scientists and physicians have tried to give chemotherapy at lower doses for more days, called "metronomic" chemotherapy. This method of giving chemotherapy has been used to treat neuroblastoma that has failed more standard types of treatment (relapsed neuroblastoma) and has shown some promise for those patients. One of the reasons it may work is by killing the blood vessels that feed the tumor as well as killing tumor cells themselves (the way that burst chemotherapy works). We think that giving a burst of chemotherapy together with metronomic therapy may kill the tumor while decreasing the side effects that we have seen in the past.
Read more
Treatment for high risk neuroblastoma usually occurs in 3 stages: induction, consolidation, and maintenance. During the induction phase, patients will receive chemotherapy and possibly more surgery to get rid of most of the tumor cells. Most of the chemotherapy drugs during induction will be given in the standard burst method. One of the chemotherapy drugs, etoposide, will be given in lower, metronomic doses. The doctors will study how the tumors respond and the side effects patients have. After induction most childrens' tumors will have disappeared, also called remission. These children will receive the second stage of treatment called consolidation. During this stage, subjects will receive radiation treatments to the tumor and then higher doses of chemotherapy. Because of the side effects of the high doses of chemotherapy, we will collect and store some special blood cells (called hematopoietic stem cells) early in treatment and keep them frozen. After the high doses of chemotherapy, these cells will be thawed and given to the subject. . This is called hematopoietic stem cell transplant (HSCT). The final stage of treatment, called maintenance, consists of a drug taken by mouth for 6 months.
Surgery to remove large, or bulky, tumors is a standard part of treatment for high risk neuroblastoma. A few children can have their main tumor removed before chemotherapy, but most require the tumor to shrink first. Surgery has usually been scheduled for after 3 to 5 cycles of therapy, but no one really knows how quickly the tumors are ready to come out. Because chemotherapy has significant side effects that can change the risks of surgery, we will study how early surgeries to remove tumors can happen.
This study is being done to evaluate the outcomes of disease response and survival in children with high risk neuroblastoma treated on this regimen.
Read the detailed description
Induction Phase Overview The induction phase is approximately 15 weeks long. Chemotherapy is generally given every 3 weeks, each 3 week block is called a "cycle". During these 15 weeks we will treat subjects with chemotherapy 5 times using combinations of 4 different chemotherapy drugs. All IV chemotherapy drugs will be given in the hospital. During this 15 weeks doctors will try to collect special blood cells called hematopoietic stem cells. If the subject's tumor has not been removed completely you will have a surgery to take the rest of the tumor out as soon as possible once it has shrunk with the first two cycles of chemotherapy.
Induction Phase Chemotherapy During the first 2 cycles of chemotherapy all children will receive two drugs: cisplatin and etoposide. Cisplatin is given through an IV for everyone. If participating in the research treatment plan, etoposide by mouth mouth for 14 days. After the first two cycles we will repeat studies to see if the tumor has shrunk. Then all children will receive two other chemotherapy drugs called cyclophosphamide and adriamycin during the 3rd cycle. If the subject responded to the first two cycles, the 4th cycle will be IV cisplatin and oral etoposide again; if the subject did not respond to the first two cycles, the 4th cycle will be IV cisplatin with standard IV etoposide. The 5th cycle will again be adriamycin and cyclophosphamide.
If subjects choose not to participate in the research treatment plan, or are not eligible for the research treatment plan, cycle 1, 2, and 4 will be IV Cisplatin and IV Etoposide.
Here is the induction treatment:
Treatment #1, 2, and 4:
Cisplatin and etoposide: Cisplatin will be given once a day for 5 days through an IV. Etoposide will be given either by mouth once a day for 14 days (research treatment plan) or through an IV for 3 days (standard treatment plan).
Treatment #3 and 5: Cyclophosphamide and adriamycin: Cyclophosphamide and adriamycin are given daily for 2 days, both drugs are given through an IV. Cyclophosphamide may cause irritation of the bladder so another drug called mesna will be given several times after each dose to help prevent this.
After treatment #3 and #5 patients will receive a drug called G-CSF. It stimulates the body to make white blood cells (infection fighting cells) to help prevent infections that can happen because of chemotherapy. G-CSF is an injection that must be given daily.
Surgery: If the primary tumor was not removed before chemotherapy,subjects will undergo a second surgery after receiving chemotherapy. Tumor reevaluation is after cycle #2 and if it is resectable subjects will have surgery at that time. If this is not possible images of the tumor will be taken after cycle #3 and again after cycle #5. Surgery will occur as soon as the tumor is resectable
Stem Cell Harvest Stem cells are special cells that can make all the different types of blood cells. Usually they are found in the bone marrow, but after chemotherapy many more of them are in your blood stream. Between the third and fifth cycles of induction, stem cells will be collected from the blood using a procedure called apheresis. The central line or catheter is connected to a machine that draws some of the subjects blood out of one side of the catheter, filters out the stem cells, and returns the rest of the blood through the other side of the catheter. Each apheresis procedure takes about 4-6 hours. The procedure may need to be done several times to collect enough stem cells.
The consolidation phase takes approximately 15 weeks to complete and consists of radiation to the tumor followed by high doses of chemotherapy and hematopoietic stem cell transplant.
HERE IS THE TREATMENT PLAN:
Local Tumor Radiation:
Local radiation therapy is given daily for about 2 weeks. Radiation beams will be aimed at the sites of the tumor. Each child's treatment will be designed just for them. The doctor who gives radiation will discuss the therapy in detail. Some children require sedation for radiation therapy. Radiation therapy does not usually require admission to the hospital.
High Dose Chemotherapy and Hematopoietic Stem Cell Transplant Carboplatin, etoposide and melphalan: Carboplatin and etoposide are given daily for 4 days followed by melphalan for 3 days. Stem cells will be infused after chemotherapy.
After high dose therapy subjects will receive G-CSF to help stimulate the growth of white blood cells. Other drugs will be used during and after the chemotherapy to prevent or decrease side effects from this treatment. Until the stem cells restore safe levels of blood cells, subjects will need to be hospitalized. This treatment may require hospitalization for 3 to 4 weeks or longer.
Maintenance Phase Starting approximately 3 months following stem cell transplant subjects will receive six monthly treatments with 13-cis-retinoic acid. 13-cis retinoic acid is a drug closely related to vitamin A and has been shown to help stop the multiplication of any remaining neuroblastoma cells in the body. This drug will be taken 2 times a day by mouth for 14 days and then not take it for the following 14 days. This 28-day cycle will be repeated 6 times.
AFTER COMPLETING STUDY TREATMENT The consolidation phase of treatment for high risk neuroblastoma lasts about 4 months. The entire treatment will last about 12-14 months.
- Conditions
- Neuroblastoma
- Being tested
- Protracted Oral Etoposide, Doxorubicin, IV Bolus Etoposide, Cisplatin, Cyclophosphamide
- Keywords
- Neuroblastoma, Etoposide, Cisplatin, Adriamycin, Cyclophosphamide, Cytoxan
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protracted Oral EtoposideDrug
Cisplatin with Oral Protracted Etoposide for cycles 1, 2 and 4
Day 1 - 5
- Hour 0: Etoposide 50 mg/m2 po daily
- Hours 1 to 7: Cisplatin 40 mg/m2
Day 6 - 14
- Etoposide 50 mg/m2 po once daily
DoxorubicinDrug
Given together with cyclophosphamide for cycle 3 and 5 of induction chemotherapy Day 1 and 2
- Hours 0 to 6: Cyclophosphamide 2000 mg/m2 (67 mg/kg if < 12 kg) with Mesna 400 mg/m2 (13 mg/kg if < 12 kg) in D5½NS 600 mL/m2 IV over 6 hours to run at 100 mL/m2/hr
- Hours 6 to 6.25: Doxorubicin 37.5 mg/m2 (1.25 mg/kg if < 12 kg) IV over 15 minutes
IV Bolus EtoposideDrug
Cisplatin with Bolus IV Etoposide
Day 1
Hours 0 to 6: Cisplatin 40 mg/m2
Days 2, 3, 4:
Hours 0 to 1: Etoposide 200 mg/m2 Hours 1 to 7: Cisplatin 40 mg/m2
Day 5:
Hours 0 to 6: Cisplatin 40 mg/m2
CisplatinDrug
Cycle 1, 2, and 4
CyclophosphamideDrug
Cycle 3 and 5 with doxorubicin
MesnaDrug
Standard weight-based dosing with cyclophosphamide
Hematopoietic FactorDrug
Standard weight-based dosing after cycle 3 and 5 and if needed for neutropenic recovery after cycles 1,2 and 4
Primary tumor resectionProcedure or surgery
Resection of primary tumor after cycle 3, 4, or 5 as clinically appropriate
| Study group | Role | What they receive |
|---|---|---|
| Protracted Oral Etoposide | Experimental | Protracted oral etoposide for cycles 1, 2 and 4 of induction. Etoposide will be given in combination with IV cisplatin (a standard of care agent). If a subject does not respond after cycle 2, cycle 4 will be bolus etoposide in combination with IV cisplatin.
All patients will receive Adriamycin and cyclophosphamide for cycle 3 and 5 as a standard of care. Receives: Drug: Protracted Oral Etoposide; Drug: Doxorubicin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Mesna; Drug: Hematopoietic Factor; Procedure: Primary tumor resection |
| IV Bolus Etoposide | Active comparator | IV bolus etoposide in combination with IV cisplatin will be given for cycles 1,2, and 4 of induction chemotherapy for patients who are not eligible for the experimental arm (e.g.require emergent treatment)
All patients will receive Adriamycin and cyclophosphamide for cycle 3 and 5 as a standard of care. Receives: Drug: Doxorubicin; Drug: IV Bolus Etoposide; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Mesna; Drug: Hematopoietic Factor; Procedure: Primary tumor resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate Associated With Two Cycles of Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma Tumors.
Partial response or better
Measured: 2 months
Rate of Toxicities Associated With Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma.
If a patient experiences any one of the following toxicities, attributed to induction chemotherapy cycles 1, or 2, that patient will be counted as having a dose limiting toxicity. 13.2.1.1 Inability to achieve ANC > 750 by Day 35 from start of chemotherapy cycle 1 or 2 (unless documented tumor involvement of marrow) 13.2.1.2 Inability to achieve platelet count at least 75,000 by Day 35 from start of chemotherapy cycle 1 or 2 (unless documented tumor involvement of marrow) 13.2.1.3 Any Grade 2 or greater toxicity non-hematopoietic/non-mucosal (mucositis/stomatitis) that is not reversible to Grade 1 or baseline by day 21 from start of chemotherapy cycle excluding Hematopoietic toxicity Mucositis/stomatitis Anorexia, nausea, vomiting Febrile neutropenia
Measured: 2 months
Secondary outcomes (3)
Overall Survival in Children With High Risk Neuroblastoma Treated on This Regimen.
Measured: 3 years
Number of Patients Who Have Surgery After the Second Cycle of Induction Therapy
the measure is the number of patients who have surgery after two cycles of induction
Measured: 2 months
Event Free Survival in Children With High Risk Neuroblastoma Treated on This Regimen.
The first of the two events (relapse or death) was chosen to represent disease free survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2007 (estimated)
- Study startMar 2007
- Primary completionJul 2009
- Study completionMar 2015
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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, Heidi Russell, Baylor College of Medicine
- Investigators
- Peter Zage, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00578864
- Sponsor's protocol ID
- H20255
- Other IDs
- PEPI
- Acronym
- PEPI
- Status last verified
- Mar 2020
- First submitted
- 19 Dec 2007
- Last updated
- 27 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PEPI: Protracted Etoposide in a Phase II Upfront Window for Induction Therapy for High Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT00578864
- Acronym / sponsor ID
- PEPI / H20255
- Conditions
- Neuroblastoma
- Keywords
- Neuroblastoma, Etoposide, Cisplatin, Adriamycin, Cyclophosphamide, Cytoxan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 21 Dec 2007 (estimated)
- Results
- Posted 6 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High-risk neuroblastoma is an aggressive childhood cancer that shows up as a lump or mass in the belly or around the spinal cord in the chest, neck, or pelvis. Often the tumor has spread around the body to the bones or to the soft center of the bone, called the bone marrow. High-risk neuroblastoma often responds to treatment at first, but it frequently comes back and may be even more difficult to treat.
Chemotherapy (drug treatments for cancer) is usually given at high doses in short bursts (3 to 5 days) followed by a few weeks of rest and recovery. This burst and recovery is called a "cycle" and usually takes about 21 days. Some scientists and physicians have tried to give chemotherapy at lower doses for more days, called "metronomic" chemotherapy. This method of giving chemotherapy has been used to treat neuroblastoma that has failed more standard types of treatment (relapsed neuroblastoma) and has shown some promise for those patients. One of the reasons it may work is by killing the blood vessels that feed the tumor as well as killing tumor cells themselves (the way that burst chemotherapy works). We think that giving a burst of chemotherapy together with metronomic therapy may kill the tumor while decreasing the side effects that we have seen in the past.
Treatment for high risk neuroblastoma usually occurs in 3 stages: induction, consolidation, and maintenance. During the induction phase, patients will receive chemotherapy and possibly more surgery to get rid of most of the tumor cells. Most of the chemotherapy drugs during induction will be given in the standard burst method. One of the chemotherapy drugs, etoposide, will be given in lower, metronomic doses. The doctors will study how the tumors respond and the side effects patients have. After induction most childrens' tumors will have disappeared, also called remission. These children will receive the second stage of treatment called consolidation. During this stage, subjects will receive radiation treatments to the tumor and then higher doses of chemotherapy. Because of the side effects of the high doses of chemotherapy, we will collect and store some special blood cells (called hematopoietic stem cells) early in treatment and keep them frozen. After the high doses of chemotherapy, these cells will be thawed and given to the subject. . This is called hematopoietic stem cell transplant (HSCT). The final stage of treatment, called maintenance, consists of a drug taken by mouth for 6 months.
Surgery to remove large, or bulky, tumors is a standard part of treatment for high risk neuroblastoma. A few children can have their main tumor removed before chemotherapy, but most require the tumor to shrink first. Surgery has usually been scheduled for after 3 to 5 cycles of therapy, but no one really knows how quickly the tumors are ready to come out. Because chemotherapy has significant side effects that can change the risks of surgery, we will study how early surgeries to remove tumors can happen.
This study is being done to evaluate the outcomes of disease response and survival in children with high risk neuroblastoma treated on this regimen.
Detailed description
Induction Phase Overview The induction phase is approximately 15 weeks long. Chemotherapy is generally given every 3 weeks, each 3 week block is called a "cycle". During these 15 weeks we will treat subjects with chemotherapy 5 times using combinations of 4 different chemotherapy drugs. All IV chemotherapy drugs will be given in the hospital. During this 15 weeks doctors will try to collect special blood cells called hematopoietic stem cells. If the subject's tumor has not been removed completely you will have a surgery to take the rest of the tumor out as soon as possible once it has shrunk with the first two cycles of chemotherapy.
Induction Phase Chemotherapy During the first 2 cycles of chemotherapy all children will receive two drugs: cisplatin and etoposide. Cisplatin is given through an IV for everyone. If participating in the research treatment plan, etoposide by mouth mouth for 14 days. After the first two cycles we will repeat studies to see if the tumor has shrunk. Then all children will receive two other chemotherapy drugs called cyclophosphamide and adriamycin during the 3rd cycle. If the subject responded to the first two cycles, the 4th cycle will be IV cisplatin and oral etoposide again; if the subject did not respond to the first two cycles, the 4th cycle will be IV cisplatin with standard IV etoposide. The 5th cycle will again be adriamycin and cyclophosphamide.
If subjects choose not to participate in the research treatment plan, or are not eligible for the research treatment plan, cycle 1, 2, and 4 will be IV Cisplatin and IV Etoposide.
Here is the induction treatment:
Treatment #1, 2, and 4:
Cisplatin and etoposide: Cisplatin will be given once a day for 5 days through an IV. Etoposide will be given either by mouth once a day for 14 days (research treatment plan) or through an IV for 3 days (standard treatment plan).
Treatment #3 and 5: Cyclophosphamide and adriamycin: Cyclophosphamide and adriamycin are given daily for 2 days, both drugs are given through an IV. Cyclophosphamide may cause irritation of the bladder so another drug called mesna will be given several times after each dose to help prevent this.
After treatment #3 and #5 patients will receive a drug called G-CSF. It stimulates the body to make white blood cells (infection fighting cells) to help prevent infections that can happen because of chemotherapy. G-CSF is an injection that must be given daily.
Surgery: If the primary tumor was not removed before chemotherapy,subjects will undergo a second surgery after receiving chemotherapy. Tumor reevaluation is after cycle #2 and if it is resectable subjects will have surgery at that time. If this is not possible images of the tumor will be taken after cycle #3 and again after cycle #5. Surgery will occur as soon as the tumor is resectable
Stem Cell Harvest Stem cells are special cells that can make all the different types of blood cells. Usually they are found in the bone marrow, but after chemotherapy many more of them are in your blood stream. Between the third and fifth cycles of induction, stem cells will be collected from the blood using a procedure called apheresis. The central line or catheter is connected to a machine that draws some of the subjects blood out of one side of the catheter, filters out the stem cells, and returns the rest of the blood through the other side of the catheter. Each apheresis procedure takes about 4-6 hours. The procedure may need to be done several times to collect enough stem cells.
The consolidation phase takes approximately 15 weeks to complete and consists of radiation to the tumor followed by high doses of chemotherapy and hematopoietic stem cell transplant.
HERE IS THE TREATMENT PLAN:
Local Tumor Radiation:
Local radiation therapy is given daily for about 2 weeks. Radiation beams will be aimed at the sites of the tumor. Each child's treatment will be designed just for them. The doctor who gives radiation will discuss the therapy in detail. Some children require sedation for radiation therapy. Radiation therapy does not usually require admission to the hospital.
High Dose Chemotherapy and Hematopoietic Stem Cell Transplant Carboplatin, etoposide and melphalan: Carboplatin and etoposide are given daily for 4 days followed by melphalan for 3 days. Stem cells will be infused after chemotherapy.
After high dose therapy subjects will receive G-CSF to help stimulate the growth of white blood cells. Other drugs will be used during and after the chemotherapy to prevent or decrease side effects from this treatment. Until the stem cells restore safe levels of blood cells, subjects will need to be hospitalized. This treatment may require hospitalization for 3 to 4 weeks or longer.
Maintenance Phase Starting approximately 3 months following stem cell transplant subjects will receive six monthly treatments with 13-cis-retinoic acid. 13-cis retinoic acid is a drug closely related to vitamin A and has been shown to help stop the multiplication of any remaining neuroblastoma cells in the body. This drug will be taken 2 times a day by mouth for 14 days and then not take it for the following 14 days. This 28-day cycle will be repeated 6 times.
AFTER COMPLETING STUDY TREATMENT The consolidation phase of treatment for high risk neuroblastoma lasts about 4 months. The entire treatment will last about 12-14 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protracted Oral Etoposide | Experimental | Drug: Protracted Oral Etoposide, Drug: Doxorubicin, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Mesna, Drug: Hematopoietic Factor, Procedure: Primary tumor resectionProtracted oral etoposide for cycles 1, 2 and 4 of induction. Etoposide will be given in combination with IV cisplatin (a standard of care agent). If a subject does not respond after cycle 2, cycle 4 will be bolus etoposide in combination with IV cisplatin. All patients will receive Adriamycin and cyclophosphamide for cycle 3 and 5 as a standard of care. |
| IV Bolus Etoposide | Active comparator | Drug: Doxorubicin, Drug: IV Bolus Etoposide, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Mesna, Drug: Hematopoietic Factor, Procedure: Primary tumor resectionIV bolus etoposide in combination with IV cisplatin will be given for cycles 1,2, and 4 of induction chemotherapy for patients who are not eligible for the experimental arm (e.g.require emergent treatment) All patients will receive Adriamycin and cyclophosphamide for cycle 3 and 5 as a standard of care. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Pts can be enrolled but receive standard etoposide bolus dosing based on clinical conditions at diagnosis (need for emergency intervention because of renal, neurologic, or airway compromise). Pts who meet all other eligibility criteria may also choose to participate in the clinical trial w/o receiving the upfront window protracted dosing of etoposide; these children will receive standard etoposide bolus dosing.
- Less than 18 yo at diagnosis
- DIAGNOSIS Neuroblastoma or ganglioneuroblastoma verified by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
- Pts with newly diagnosed neuroblastoma and age 365 or more days with the following: INSS Stage 2a/2b with MYCN amplification , AND unfavorable pathology INSS Stage 3 with MYCN amplification AND/OR unfavorable pathology
- Pts with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following: Age more than 18 months (greater than 547 days) regardless of biologic features Age 12 to 18 months (365-547 days) with any unfavorable biologic feature (MYCN amplification, unfavorable pathology and/or DNA index equal to 1) or any biologic feature that is indeterminant/unsatisfactory/unknown.
Key exclusion criteria (6 listed)
- Patients who do not meet inclusion criteria.
- Patients who are pregnant or lactating are not eligible.
- EXCLUSION CRITERIA UPFRONT WINDOW Patients can be enrolled onto Stratum 1 but receive standard etoposide bolus dosing based on clinical conditions at diagnosis. Patients who meet all other eligibility criteria may also choose to participate in the clinical trial without receiving the upfront window protracted dosing of etoposide; these children will receive standard etoposide bolus dosing.
- Patients whose tumor requires emergency intervention because of spinal cord compression, CNS compromise, or airway compromise.
- Patients requiring dialysis.
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 |
|---|---|---|
| Protracted Oral EtoposideCisplatin with Oral Protracted Etoposide for cycles 1, 2 and 4 Day 1 - 5 * Hour 0: Etoposide 50 mg/m2 po daily * Hours 1 to 7: Cisplatin 40 mg/m2 Day 6 - 14 * Etoposide 50 mg/m2 po once daily | Drug | Protracted Oral Etoposide |
| DoxorubicinGiven together with cyclophosphamide for cycle 3 and 5 of induction chemotherapy Day 1 and 2 * Hours 0 to 6: Cyclophosphamide 2000 mg/m2 (67 mg/kg if < 12 kg) with Mesna 400 mg/m2 (13 mg/kg if < 12 kg) in D5½NS 600 mL/m2 IV over 6 hours to run at 100 mL/m2/hr * Hours 6 to 6.25: Doxorubicin 37.5 mg/m2 (1.25 mg/kg if < 12 kg) IV over 15 minutes | Drug | IV Bolus Etoposide, Protracted Oral Etoposide |
| IV Bolus EtoposideCisplatin with Bolus IV Etoposide Day 1 Hours 0 to 6: Cisplatin 40 mg/m2 Days 2, 3, 4: Hours 0 to 1: Etoposide 200 mg/m2 Hours 1 to 7: Cisplatin 40 mg/m2 Day 5: Hours 0 to 6: Cisplatin 40 mg/m2 | Drug | IV Bolus Etoposide |
| CisplatinCycle 1, 2, and 4 | Drug | IV Bolus Etoposide, Protracted Oral Etoposide |
| CyclophosphamideCycle 3 and 5 with doxorubicin | Drug | IV Bolus Etoposide, Protracted Oral Etoposide |
| MesnaStandard weight-based dosing with cyclophosphamide | Drug | IV Bolus Etoposide, Protracted Oral Etoposide |
| Hematopoietic FactorStandard weight-based dosing after cycle 3 and 5 and if needed for neutropenic recovery after cycles 1,2 and 4 | Drug | IV Bolus Etoposide, Protracted Oral Etoposide |
| Primary tumor resectionResection of primary tumor after cycle 3, 4, or 5 as clinically appropriate | Procedure or surgery | IV Bolus Etoposide, Protracted Oral Etoposide |
Primary outcome
Response Rate Associated With Two Cycles of Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma Tumors.
Time frame: 2 months
Partial response or better
Rate of Toxicities Associated With Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma.
Time frame: 2 months
If a patient experiences any one of the following toxicities, attributed to induction chemotherapy cycles 1, or 2, that patient will be counted as having a dose limiting toxicity. 13.2.1.1 Inability to achieve ANC > 750 by Day 35 from start of chemotherapy cycle 1 or 2 (unless documented tumor involvement of marrow) 13.2.1.2 Inability to achieve platelet count at least 75,000 by Day 35 from start of chemotherapy cycle 1 or 2 (unless documented tumor involvement of marrow) 13.2.1.3 Any Grade 2 or greater toxicity non-hematopoietic/non-mucosal (mucositis/stomatitis) that is not reversible to Grade 1 or baseline by day 21 from start of chemotherapy cycle excluding Hematopoietic toxicity Mucositis/stomatitis Anorexia, nausea, vomiting Febrile neutropenia
3 secondary outcomes
Overall Survival in Children With High Risk Neuroblastoma Treated on This Regimen.
Time frame: 3 years
Number of Patients Who Have Surgery After the Second Cycle of Induction Therapy
Time frame: 2 months
Event Free Survival in Children With High Risk Neuroblastoma Treated on This Regimen.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 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.
Peter Zage, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Protracted Oral Etoposide, Doxorubicin and IV Bolus Etoposide in people with Neuroblastoma, run by Baylor College of Medicine at 1 site 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 19 inclusion and 6 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 27 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 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2012). 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?
Response Rate Associated With Two Cycles of Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma Tumors. (time frame: 2 months). The study lists 2 primary outcomes in all. 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 27 Mar 2020.