Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue Followed by 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors

Brain Tumors Clinical Trial

Official title:

NYU 05-40 PBMTC ONC-032P:High Dose Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue (ASCR) Followed by Continuation Therapy With 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528437
• Other study ID #: 12853
• Secondary ID: PBMTC ONC-032P
• Status: Completed
• Phase: Phase 2
• Start date: October 2005
• Est. completion date: December 30, 2017

Study information

• Verified date: June 2021
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to:

Find out how safe and effective (by monitoring the good and/or bad effects) treatment with high dose temozolomide, thiotepa and carboplatin with stem cell rescue followed by 13-cis-retinoic acid has on children and adolescents with recurrent/refractory brain tumors

Find out how the body uses 13-cis-retinoic acid by studying the your blood levels and proteins in the blood that break down the 13-cis-retinoic acid

Determine how well 13-cis-retinoic acid penetrates into the spinal fluid.

Description:

Researchers have used high doses of combination chemotherapy followed by a stem cell rescue to treat recurrent brain tumors with moderate success. High dose chemotherapy with stem cell rescue has resulted in long term survival of about 25% in patients with several different types of recurrent brain tumors. Stem cells are cells in the bone marrow that produce blood cells. The stem cells are collected from the blood of the patient before the high dose chemotherapy. Patients are given high doses of chemotherapy to kill every brain tumor cell, but in the process the cells of the bone marrow are also killed. The previously collected stem cells are then infused into the patient to rescue the bone marrow and allow for healthy blood cells to re-populate and grow in the bone marrow. Initial studies used the drug etoposide along with carboplatin and thiotepa for the high dose chemotherapy. Patients had severe side effects, especially severe mouth-sores, thought mainly due to the etoposide, and some patients died from these side effects.

Recent studies have shown that a new drug, temozolomide, is active against some types of brain tumors. When it was given as a single drug to children with solid tumors, the side effects were considered to be tolerable. Temozolomide is given by mouth. In this study, researchers want to give high dose chemotherapy that includes the drugs temozolomide in place of etoposide, along with thiotepa and carboplatin. Patients will then be given their own stem cells back to rescue the bone marrow from the chemotherapy. A preliminary trial using this new drug combination was performed and has shown that patients tolerate this drug combination, even at the very high doses that will be used in this protocol.

Another drug that is being used in pediatric cancer treatment is called 13-cis-retinoic acid. This drug is closely related to vitamin A. It is taken by mouth. Cancer cells are immature cells that have not "grown up" into adult cells that do work in the body. 13-cis-retinoic acid is thought to act on some types of cancer cells to make them mature into cells that function in the body. It has also been shown in the laboratory to cause some brain tumor cells to undergo apoptosis. It has been used in other types of pediatric cancers and research is just beginning to use it for treatment of recurrent brain tumors. In this study researchers want to give you 13-cis-retinoic acid for 6 months after you recover from the high dose chemotherapy with stem cell rescue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

Inclusion Criteria:

1. Patients with recurrent or refractory medulloblastoma/PNET, CNS germ cell tumors, ependymomas, AT/RT, high grade glioma and other malignant brain tumors. Brainstem gliomas are eligible if residual disease is < 1.5cc and if the patient is off decadron.

2. Patients must have recurrent or refractory disease following at least one prior course of therapy and must have minimal residual disease defined as < 1.5 cm2 of enhancement. Patients with + CSF cytology, linear or fine nodular leptomeningeal disease are eligible.

3. Adequate hematologic, renal, liver, and cardiac function as demonstrated by laboratory values performed within 21 days, inclusive, prior to administration of temozolomide.

4. Patients must have an adequate number of autologous stem cells available defined as a minimum of 2 x 106 CD 34+ cells/kg and preferably at least 5 x 106 CD 34+ cells/kg.

Exclusion Criteria:

1. Previous myeloablative therapy

2. Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction)

3. Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. Patients with prior malignancies which have not required anti-tumor treatment within the preceding 24 months are eligible.

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors

Intervention

Drug:
• temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
13-cis-retinoic acid, when absorbed, may be subject to first-pass metabolism and subsequent plasma (and tumor) concentrations will depend on the rate of metabolism to the inactive 4-oxo metabolite.

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Emory University	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical Univ. of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	MD Anderson Cancer Center (MDACC)	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Hawaii Pacific Health	Lihue	Hawaii
United States	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Univ.	Nashville	Tennessee
United States	Steven and Alexandra Cohen Children's Medical Center of New York- North Shore LIJ	New Hyde Park	New York
United States	NYU Hassenfeld Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Virginia Commonwealth Univ.	Richmond	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
NYU Langone Health	Children's Hospitals and Clinics of Minnesota, Schneider Children's Hospital

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS)	EFS will be reported in patients with recurrent or refractory medulloblastoma/ primitive neuroectodermal tumors. EFS is defined as the length of time after primary treatment for a cancer ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay.	Day +42
Primary	Overall Survival (OS)	OS will be reported in patients with recurrent or refractory medulloblastoma/ primitive neuroectodermal tumors. OS is defined as the length of time from the start of treatment that patients diagnosed with disease are still alive.	Day +77
Secondary	Toxicity of of 13-cis-retinoic Acid	To report the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR.	One year