MDACC Study Summary 2007-0028

Study Summary
No. 2007-0028:.......Blood And Marrow Transplantation; Brain; Pediatrics......Laura L. Worth......Pediatrics

Study Summary Title



Study Summary Number:	2007-0028

Study Title:	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

Physician

New Patient Referral



Name:	Laura L. Worth	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Pediatrics	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6620 Contact us about clinical trials

General Information



Disease Group:	Blood And Marrow Transplantation Brain Pediatrics	Supported By:	Pediatric Blood and Marrow Transplant Consortium

Phase of Study:	Phase II	Return Visit:	Twice weekly for up to 2 months post transplant

Treatment Agents:	13-Cis Retinoic Acid Carboplatin Temozolomide Thiotepa	Home Care:	There is a possible need for IV fluids and antibiotics at home. Subject will receive the 13-cis-retinoic acid by mouth twice a day. It is given for 14 days followed by a 14 day rest period. Cycle is given 6 times for a total of 6 months of treatment.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	The subject will be hospitalized one or two nights during the apheresis process (if requires a femoral catheter). During the autologous BMT - approximately 3-4 weeks. Outpatient - must remain in the area for days after stem cell infusion

Description/
Intervention:

The goal of this clinical research study is to learn the effects of
temozolomide, thiotepa, and carboplatin with a stem cell transplant followed by
13-cis-retinoic acid (isotretinoin) in children and adolescents with brain
tumors that have not responded to treatment or have come back after treatment.

Researchers also hope to learn how the body uses isotretinoin and how well it
absorbs into the spinal fluid.

Study Objectives / Outcomes

Primary:

To assess the event-free survival (EFS) and overall survival (OS) of patients with recurrent or refractory medulloblastoma/primitive neuroectodermal tumors (PNET) with minimal residual disease treated with high dose temozolomide, thiotepa, and carboplatin with ASCR followed by continuation therapy with 13-cis-retinoic acid.

Secondary

To assess the EFS and OS of patients with recurrent or refractory central nervous system germ cell tumor (CNS GCT), high grade glioma, brainstem glioma, ependymoma, atypical teratoid/rhabdoid tumor (ATRT) and other high grade malignant brain tumors (excluding high grade gliomas ) with minimal residual disease treated with high dose temozolomide, thiotepa, and carboplatin with ASCR followed by continuous therapy with 13-cis-retinoic acid.
To evaluate the toxicity of high dose temozolomide, thiotepa, and carboplatin with ASCR when performed in a multi-institutional setting.
To evaluate the toxicity of 13-cis-retinoic acid following high dose temozolomide, thiotepa, and carboplatin with ASCR
To assess the inter-individual variability in plasma pharmacokinetics of 13-cis-retinoic acid and assess a single CSF 13-cis-retinoic acid level to determine if it is a potential indicator of CNS penetration go the drug.
To investigate the influence of genetic variation in enzymes involved in the metabolism of 13-cis-retinoic acid on the pharmacokinetics of this agent
To relate inter-individual variability in the pharmacokinetics of 13-cis-retinoic acid and genetic variation to clinical response as measured by event-free survival and toxicity.

Study Status Information



Study Activation / Registration Date:	01/26/2009

IRB Review and Approval Date:	02/18/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	75

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 </=1.5 cc 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 as defined as </= 1.5cm^2 of enhancement. Patients with + CSF cytology, linear or fine nodular leptomeningeal disease are eligible.

3) Karnofsky Performance Status or Lansky Performance score >/= 70%

4) Anticipated life expectancy > 12 weeks to be eligible for this study

5) Adequate hematologic, renal, liver, and cardiac function as demonstrated by laboratory values within 21 days, inclusive, prior to administration of temezolomide. ANC >/= 750/mm^3; platelet count >/= 50,000/mm^3; Hgb >/=10 gm/dL (Patients may be transfused to raise the hemoglobin above 10 gm/dl), BUN and Cr <1.5 X upper limits of normal, Creatinine claearance or GFR >/= 70 cc/min/1.73 m^2. Total serum bilirubin <1.5 upper limits, SGPT <2.5 X upper limits of normal.

6) Patient must have an adequate number of autologus stem cells available, defined as a minimum of 2 x 10^6 CD34+ cells/kg and preferably at least 5 x 10^6 CD34+ cells/kg.

7) Age greater than 6 months and less than 21 years.

8) Patients must have recovered from any effects of major surgery, chemotherapy, or radiation. Patients must not have received chemotherapy (excluding nitrosureas) with in 21 days and may not have received radiation therapy therapy or nitroureas within 42 days of starting treatment.

9) Patients may have received stereotactic radiation at the time of recurrence as part of their salvage treatment.

10) Patients or legal guardians must give written informed consent. Patients between the ages of 7 and 18 must give assent, or have documentation supporting why this is not obtained.

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 malignancy at other sites with the exception of surgically cured carcinoma-in-situ of the cervis and basal or squamous cell carcinoma of the skin. Patients with prior malignancies which have not required anti-tumor treatment with in the the preceeding 24 month are eligible.

4) Known HIV positivity or AIDS-related illness.

5) Pregnant or nursing women.

6) Women of childbearing potential who are not using an effective method of contraception.

7) Men who refuse to use an effective method of contraception.

8) Institutional Human Rights Committee/Institutional Review Board approval: Approval for the use of this treatment regimen by the individual's Human Rights Committee or Institutional Review Board (IRB) must be obtained in accordance with the individual institutional assurance policies of the United States DHHS and must be one file at the New York University Pediatric Oncology Trials Office prior to enrollment of any patient on study.

9) Registration: Patients will enter on study at time protocol therapy is planned to begin. Eligible patients will be registered by contacting Rosa Chu in the Pediatric Oncology Clinical Trials Office at NYU M-F 9am-5pm EST at (212)263-9924 except holidays. The info. requested on the protocol eligibility form must be completed and the signed informed consent for protocol therapy must be faxed to (212)263-8410 at time of phone call for registration to occur. Patients must be registered prior to starting protocol therapy. Email confirming eligibility will be sent to treating institution.

Links

Registration Number: NCT00528437
Study Information on Clinical Trials Registry (clinicaltrials.gov)