Brain TumorsPhase 2NCT00528437
Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue Followed by 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors
A Phase 2 study testing temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid in people with Brain Tumors, run by NYU Langone Health at 17 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Brain Tumors
- What is being tested?
- temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 17 sitesin 2 countries
- Study dates
- Oct 2005to 30 Dec 2017
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States16 sites
Emory University
Atlanta, Georgia, 30322
Roswell Park Cancer Institute
Buffalo, New York, 14263
Medical Univ. of South Carolina
Charleston, South Carolina, 29425
Children's Memorial Hospital
Chicago, Illinois, 60614
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Medical Center of Dallas
Dallas, Texas, 75235
MD Anderson Cancer Center (MDACC)
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Hawaii Pacific Health
Lihue, Hawaii, 96766
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Vanderbilt Univ.
Nashville, Tennessee, 37240
Steven and Alexandra Cohen Children's Medical Center of New York- North Shore LIJ
New Hyde Park, New York, 11040
NYU Hassenfeld Center
New York, New York, 10016
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Virginia Commonwealth Univ.
Richmond, Virginia, 23284
About this study
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
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.
Read the 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.
- Conditions
- Brain Tumors
- Being tested
- temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
- Keywords
- Recurrent or refractory medulloblastoma/PNET, CNS germ cell tumors, Ependymomas, AT/RT, High grade glioma, Other malignant brain tumors
- Medical subject headings
- Brain Neoplasms, Recurrence, Ependymoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temozolomide, thiotepa, carboplatin, 13-cis-retinoic acidDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin. | Other | Not described Receives: Drug: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day +42
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.
Measured: Day +77
Secondary outcomes (1)
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2007 (estimated)
- Study startOct 2005
- Primary completion30 Jun 2017
- Study completion30 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain TumorsStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospitals and Clinics of Minnesota, Schneider Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Sharon L Gardner, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00528437
- Sponsor's protocol ID
- 12853
- Other IDs
- PBMTC ONC-032P
- Status last verified
- Jun 2021
- First submitted
- 10 Sep 2007
- Last updated
- 8 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No