Clinical Trials Logo

Clinical Trial Summary

The prognosis of children and adolescents with high risk tumors of the central nervous system and other miscellaneous solid tumors is poor despite modern treatment protocols. Frequently, physicians suggest additional therapy with high dose chemotherapy after a good initial response to standard doses of treatment has been obtained, so as to reduce the chance that the tumor will recur. We propose a regimen of high dose thiotepa and melphalan followed by rescue of the patient's previously stored hematopoietic (blood manufacturing) system with blood stem cells. The aim of this study is to prove that this therapy is tolerable in children and adolescents, that it results in tolerable levels of toxicity, and that it improves the survival of this group of children as compared to standard therapy given in the past


Clinical Trial Description

Despite progress in the treatment of children and adolescents suffering from solid tumors and tumors of the CNS, patients with metastatic disease (or with disease with other high risk features) continue to suffer from relapse when treated with standard chemotherapy protocols. In these patients, high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been proposed as consolidation therapy in this high-risk population.

The paradigm for successfully utilization of autologous stem cell transplantation is childhood neuroblastoma. A large, well performed, randomized study in children with high risk neuroblastoma showed that application of autologous stem cell transplant can lead to improved disease free and overall survival, effects that were further augmented by the administration of biological agents with specific activity against this tumor. Smaller non-controlled studies and case series have shown that ASCT is feasible in children with solid tumors or with tumors of the central nervous system. Despite the many reports in the literature, there is little agreement among investigators as to the ideal combination of chemotherapeutic agents that should be included in the high dose chemotherapy regimen administered prior to ASCT for these patients. The choice of agents in these protocols is dictated by the use of drugs whose dose limiting toxicity is hematopoietic, a concern that is obviated by the subsequent infusion of autologous stem cells. As such, the majority of HDC protocols exploit the steep dose response curve of alkylating agents, where administration of high doses had usually been limited by fear of inducing permanent myeloablation.

A major limitation of many HDC protocols is that many of the alkylating agents that are used have already been utilized in front line protocols. A further problem in the design of HDC protocols that is unique to patients suffering from CNS tumors, is that the administered agents must traverse the blood brain barrier (BBB) in order to reach the site of the tumor.

A major breakthrough in the the application of HDC in children nwith CNS tumors occurred with the use of Thiotepa, a highly myeloablative bifunctional alkylating agent that partitions equally across the BBB. Thiotepa is now a mainstay of all HDC protocols for children with CNS tumors.

Hara et al. pioneered a novel combination of Thiotepa with Melpahlan, also an alkylating agent, in the treatment of children with a variety of solid tumors. They catalogued the toxicity of this protocol, and suggested a dose level of each drug in the combination that led to toxicity levels of grade ≤3. Of note, in the Hara series, some patients also received high dose Busulfan.

We piloted the Hara protocol in our center on 14 patients and found that the dose levels suggested in their study were not tolerated well by children in our center. We decided to modify the Hara protocol by reducing the doses of both Thiotepa and Melphalan to reduce the incidence of severe gastrointestinal toxicity that our patients experienced. In addition, after two patients succumbed to fulminant gram positive infections on the original protocol, we instituted the empiric administration of Vancomycin for primary treatment of febrile neutropenia in these patients, pending the results of blood cultures. We also decided to restrict admission to the protocol to patients with minimal amounts of residual disease as measured by MRI / CT scan or biochemical markers prior to transplant. ;


Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00607984
Study type Interventional
Source Rabin Medical Center
Contact Jerry Stein, MD
Phone +97239253604
Email jstein@clalit.org.il
Status Recruiting
Phase N/A
Start date June 2006

See also
  Status Clinical Trial Phase
Suspended NCT01562626 - Phase I/II Study of APS001F With Flucytosine and Maltose in Solid Tumors Phase 1/Phase 2
Completed NCT00435669 - A Phase I Study to Determine Absorption, Distribution, Metabolism, and Elimination of a Single Radiolabeled Dose of Brivanib (BMS-582664) Phase 1
Completed NCT00372437 - A Phase I/II Study of MGCD0103 (MG-0103) in Combination With Gemcitabine Phase 1/Phase 2
Completed NCT00410696 - Pegfilgrastim Versus Filgrastim After High-dose Chemotherapy Phase 2
Completed NCT00395434 - Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors Phase 1
Completed NCT00400023 - A Phase 1, Open-Label, Randomized, Cross-Over, Pharmacokinetic Study Evaluating the Effect of S-1 on Advanced Solid Tumors Phase 1
Completed NCT00375245 - Rapamycin With Grapefruit Juice for Advanced Malignancies Phase 1
Recruiting NCT00553033 - Laparoscopic Liver Resection N/A
Completed NCT00248404 - NB1011 Administered by Continuous Infusion in Cancers That Overexpress Thymidylate Synthase (TS) Phase 1/Phase 2
Completed NCT00207103 - MAD in Cancer Patients: Safety of BMS-582664 in Patients With Advanced or Metastatic Solid Tumors Phase 1
Completed NCT00222443 - Pilot Study Combining Temozolomide, Oncovin, Camptosar and Oral Antibiotic in Children and Adolescents With Recurrent Malignancy Phase 1
Terminated NCT03251924 - A Dose Escalation and Combination Immunotherapy Study to Evaluate BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT05103969 - Cohort of Tumors With POLE/D1 Mutation
Completed NCT00446446 - PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer) Phase 2
Completed NCT02275910 - Phase 1 Study of E7090 in Subjects With Solid Tumor Phase 1
Terminated NCT02271516 - to evaluate188Re-BMEDA-liposome in Patient With Primary Solid Tumor in Advanced or Metastatic Stage Phase 1
Completed NCT01448759 - Evaluation of Plasma Alcohol Concentration in Patients Receiving Paclitaxel or Docetaxel N/A
Terminated NCT01081808 - Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors Phase 1
Completed NCT00398814 - Phase I Study of Perifosine + Sorafenib for Patients With Advanced Cancers Phase 1
Completed NCT00389480 - Study of AR-67 (Formerly DB-67) in Adult Patients With Refractory or Metastatic Solid Malignancies Phase 1