Protracted Etoposide During Induction Therapy for High Risk Neuroblastoma (PEPI)
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.
|Neuroblastoma||Drug: Protracted Oral Etoposide Drug: Adriamycin and Cyclophosphamide Drug: IV Cisplatin and IV Bolus Etoposide||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||PEPI: Protracted Etoposide in a Phase II Upfront Window for Induction Therapy for High Risk Neuroblastoma|
- 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 ]
- 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. 220.127.116.11 Inability to achieve ANC > 750 by Day 35 from start of chemotherapy cycle 1 or 2 (unless documented tumor involvement of marrow) 18.104.22.168 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) 22.214.171.124 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
- Overall Survival in Children With High Risk Neuroblastoma Treated on This Regimen. [ Time Frame: 3 years ]
- Percentage of Patients Who Have Surgery After the Second Cycle of Induction Therapy [ Time Frame: 2 months ]the measure is the number of patients who have surgery after two cycles of induction
- Event Free Survival in Children With High Risk Neuroblastoma Treated on This Regimen. [ Time Frame: 3 years ]The first of the two events (relapse or death) was chosen to represent disease free survival
|Study Start Date:||March 2007|
|Study Completion Date:||March 2015|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Experimental: Protracted Oral Etoposide
Protracted etoposide for cycles 1, 2 and 4 of induction. If a subject does not respond after cycle 2, cycle 4 will be bolus etoposide.
Drug: Protracted Oral Etoposide
IV Cisplatin and Oral Protracted Etoposide for induction
Induction chemotherapy will consist of five cycles 21 days apart. Cycles 1, 2 and 4 will be IV cisplatin and etoposide. Patients on the phase II window will receive the first two cycles of chemo with IV cisplatin and oral protracted etoposide. If their tumor responds with a CR, VGPR or PR, it will be repeated during cycle 4. If their tumor does not respond cycle 4 will include bolus etoposide
Cisplatin with Oral Protracted Etoposide for cycles 1, 2 and 4
Day 1 - 5
Day 6 - 14
Active Comparator: IV Cisplatin and IV Bolus Etoposide
This arm is for patients whose tumor does not respond satisfactorily to the first two cycles of chemotherapy with IV cisplatin and oral protracted etoposide. Patients on this arm will receive cycle 4 etoposide given as a bolus IV dose.
Drug: IV Cisplatin and IV Bolus Etoposide
Induction chemotherapy will consist of five cycles of chemotherapy given 21 days apart. The 1st, 2nd and 4th cycles will the IV Cisplatin and Etoposide. Patients ineligible to participate on the phase II window will receive IV bolus etoposide during cycles 1, 2 and 4.
Cisplatin with Bolus IV Etoposide
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
Hours 0 to 6: Cisplatin 40 mg/m2
Experimental: Adriamycin and Cyclophosphamide
Induction chemotherapy will consist of 5 cycles given 21 days apart. Cycle 3 and 5 will be adriamycin and cyclophosphamide
Drug: Adriamycin and Cyclophosphamide
Induction chemotherapy will consist of 5 cycles given 21 days apart. Cycle 3 and 5 will be adriamycin and cyclophosphamide.
Day 1 and 2
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00578864
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Peter Zage, MD||Baylor College of Medicine|