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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00528437
• Collaborator: Children's Hospitals and Clinics of Minnesota (Other), Schneider Children's Hospital (Other)
• Enrollment: 46
• Locations: 17
• Arm: 1
• Actual Duration (Months): 147
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors	Drug: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Dec 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.	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.

Outcome Measures

Primary Outcome Measures

1. Event-free Survival (EFS) [Day +42]

   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.

2. Overall Survival (OS) [Day +77]

   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.

Secondary Outcome Measures

1. Toxicity of of 13-cis-retinoic Acid [One year]

   To report the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Emory University	Atlanta	Georgia	United States	30322
3	Hawaii Pacific Health	Lihue	Hawaii	United States	96766
4	Children's Memorial Hospital	Chicago	Illinois	United States	60614
5	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
6	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
7	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
8	Steven and Alexandra Cohen Children's Medical Center of New York- North Shore LIJ	New Hyde Park	New York	United States	11040
9	NYU Hassenfeld Center	New York	New York	United States	10016
10	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
11	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
12	Medical Univ. of South Carolina	Charleston	South Carolina	United States	29425
13	Vanderbilt Univ.	Nashville	Tennessee	United States	37240
14	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
15	MD Anderson Cancer Center (MDACC)	Houston	Texas	United States	77030
16	Virginia Commonwealth Univ.	Richmond	Virginia	United States	23284
17	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• NYU Langone Health
• Children's Hospitals and Clinics of Minnesota
• Schneider Children's Hospital

Investigators

• Principal Investigator: Sharon L Gardner, MD, NYU Langone Health

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Feb 18, 2011

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00528437
• Other Study ID Numbers: 12853; PBMTC ONC-032P
• First Posted: Sep 12, 2007
• Last Update Posted: Jul 8, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by NYU Langone Health: Recurrent or refractory medulloblastoma/PNET; CNS germ cell tumors; Ependymomas; AT/RT; High grade glioma; Other malignant brain tumors
• Additional relevant MeSH terms: Brain Neoplasms; Carboplatin; Temozolomide; Thiotepa; Tretinoin; Isotretinoin

Study Results

Participant Flow

Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
Period Title: Overall Study
STARTED	46
COMPLETED	46
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
Overall Participants	46
Age (Count of Participants)
<=18 years	40 87%
Between 18 and 65 years	6 13%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	15 32.6%
Male	31 67.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 15.2%
Not Hispanic or Latino	39 84.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.2%
White	25 54.3%
More than one race	0 0%
Unknown or Not Reported	19 41.3%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival (EFS)
Description	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.
Time Frame	Day +42

Outcome Measure Data

Analysis Population Description

Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
Measure Participants	0

2. Primary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Day +77

Outcome Measure Data

Analysis Population Description

Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

Title	Toxicity of of 13-cis-retinoic Acid
Description	To report the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Adverse Event Reporting Description	Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Arm/Group Title	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
Arm/Group Description	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.
All Cause Mortality
	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin.
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.