Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue Followed by 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors
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| ClinicalTrials.gov Identifier: NCT00528437 |
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Recruitment Status :
Completed
First Posted : September 12, 2007
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
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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 |
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 Type : | Interventional (Clinical Trial) |
| 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 : | October 2005 |
| Actual Primary Completion Date : | June 30, 2017 |
| Actual Study Completion Date : | December 30, 2017 |
| Arm | Intervention/treatment |
|---|---|
| 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. |
- Event-free Survival (EFS) [ Time Frame: 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.
- Overall Survival (OS) [ Time Frame: 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.
- Toxicity of of 13-cis-retinoic Acid [ Time Frame: One year ]To report the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR.
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| Ages Eligible for Study: | 6 Months to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- 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.
- Adequate hematologic, renal, liver, and cardiac function as demonstrated by laboratory values performed within 21 days, inclusive, prior to administration of temozolomide.
- 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:
- Previous myeloablative therapy
- Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction)
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00528437
Show 17 study locations
| Principal Investigator: | Sharon L Gardner, MD | NYU Langone Health |
Documents provided by NYU Langone Health:
| Responsible Party: | NYU Langone Health |
| ClinicalTrials.gov Identifier: | NCT00528437 |
| Other Study ID Numbers: |
12853 PBMTC ONC-032P ( Other Identifier: Pediatric Blood and Marrow Tranplant Consortium ) |
| First Posted: | September 12, 2007 Key Record Dates |
| Results First Posted: | July 8, 2021 |
| Last Update Posted: | July 8, 2021 |
| Last Verified: | June 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 |
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Recurrent or refractory medulloblastoma/PNET CNS germ cell tumors Ependymomas |
AT/RT High grade glioma Other malignant brain tumors |
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Brain Neoplasms Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Carboplatin Temozolomide Thiotepa Tretinoin |
Isotretinoin Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Keratolytic Agents Dermatologic Agents |