Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

Learn more about:
Related Clinical Trial
A Phase II Trial Evaluating the Efficacy of Cabozantinib With Patients With Refractory GCTs Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults Symptom Management for YA Cancer Survivors A Study of miRNA 371 in Patients With Germ Cell Tumors Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors Aflac ST0901 CHOANOME – Sirolimus in Solid Tumors Study of Genistein in Pediatric Oncology Patients (UVA-Gen001) A Pilot RCT of the PRISM Intervention for AYAs With Cancer Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors Molecular-Guided Therapy for Childhood Cancer EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors Auto Transplant for High Risk or Relapsed Solid or CNS Tumors Busulfan in Treating Children and Adolescents With Refractory CNS Cancer CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven’t Responded to Therapy ABT-751 in Treating Young Patients With Refractory Solid Tumors Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Collecting and Storing Tissue From Young Patients With Cancer Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Everolimus in Refractory Testicular Germ Cell Cancer Studying Genes in Samples From Younger Patients With Ovarian or Testicular Sex Cord Stromal Tumors Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS) A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors First Line TIP in Poor Prognosis TGCTs. Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Electroacupuncture in Treating Delayed Nausea and Vomiting in Patients Receiving Chemotherapy For Newly Diagnosed Childhood Sarcoma, Neuroblastoma, Nasopharyngeal Cancer, Germ Cell Tumors, or Hodgkin Lymphoma Disulfiram and Cisplatin in Refractory TGCTs. Role of Axumin PET Scan in Germ Cell Tumor Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors Study Evaluating the Impact of Short Message Service on Compliance With Surveillance of Patients With Germ-cell Tumors Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors Etoposide, Carboplatin, and Bleomycin in Treating Young Patients Undergoing Surgery For Malignant Germ Cell Tumors Studying Biomarkers in Samples From Younger Patients With Malignant Germ Cell Tumor Progression Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors Proton Beam Radiation Therapy for Central Nervous System (CNS) Germ Cell Tumors Germ Cell Tumor and Testicular Tumor DNA Registry A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors

Brief Title

Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

Official Title

Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors

Brief Summary

      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining more than one drug may kill more tumor cells.

      PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and
      O6-benzylguanine in treating children who have solid tumors that have not responded to
      previous therapy.
    

Detailed Description

      OBJECTIVES:

        -  Determine the maximum tolerated dose of temozolomide administered with a biologically
           active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.

        -  Determine the dose-limiting toxicity and the toxicity profile of this combination in
           these patients.

        -  Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in
           these patients.

        -  Assess the plasma pharmacokinetics of this combination in these patients.

        -  Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear
           cells with the degree of hematologic toxicity of this combination in these patients.

      OUTLINE: This is a dose-escalation study.

      Patients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral
      temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the
      absence of unacceptable toxicity or disease progression.

      Sequential dose escalation of O6-BG is followed by sequential dose escalation of
      temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide
      until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose
      preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.

      Quality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.

      PROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2 years.
    

Study Phase

Phase 1

Study Type

Interventional




Condition

Brain and Central Nervous System Tumors

Intervention

O6-benzylguanine


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug


Start Date

June 2000



Eligibility Criteria

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed solid tumor refractory to standard therapy and for which no
             potentially curative therapy exists, including, but not limited to:

               -  Rhabdomyosarcoma and other soft tissue sarcomas

               -  Ewing's family of tumors

               -  Osteosarcoma

               -  Neuroblastoma

               -  Wilms' tumor

               -  Hepatic tumors

               -  Germ cell tumors

               -  Primary brain tumor

          -  Histological confirmation may be waived for brainstem or optic gliomas

          -  Measurable or evaluable disease

          -  Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent
             disease after prior surgery

        PATIENT CHARACTERISTICS:

        Age:

          -  21 and under

        Performance status:

          -  ECOG 0-2

        Life expectancy:

          -  At least 8 weeks

        Hematopoietic:

          -  Absolute granulocyte count greater than 1,500/mm^3

          -  Hemoglobin greater than 8 g/dL

          -  Platelet count greater than 100,000/mm^3

        Hepatic:

          -  Bilirubin normal

          -  SGPT less than 2 times upper limit of normal

          -  No significant hepatic dysfunction

        Renal:

          -  Creatinine normal OR

          -  Creatinine clearance at least 60 mL/min

        Cardiovascular:

          -  No significant cardiac dysfunction

        Pulmonary:

          -  No significant pulmonary dysfunction

        Other:

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Able to swallow capsules

          -  No significant unrelated systemic illness that would preclude study (e.g., serious
             infections or organ dysfunction)

          -  No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol

        PRIOR CONCURRENT THERAPY:

        Biologic therapy:

          -  At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G- CSF],
             sargramostim [GM-CSF], or epoetin alfa)

          -  At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell
             transplantation

          -  No concurrent anticancer immunotherapy

        Chemotherapy:

          -  See Disease Characteristics

          -  At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered

          -  Prior temozolomide allowed provided not administered within past 3 months, no severe
             toxicities experienced during prior course, and not given in combination with other
             agents designed to inactivate alanine-glyoxylate aminotransferase

          -  No other concurrent investigational or standard anticancer chemotherapy

        Endocrine therapy:

          -  Concurrent corticosteroids for control of brain tumor-associated edema allowed
             provided on stable or decreasing dose for at least 1 week prior to study

        Radiotherapy:

          -  See Disease Characteristics

          -  At least 4 weeks since prior limited-field radiotherapy

          -  At least 4 months since prior craniospinal irradiation, total body irradiation, or
             radiotherapy to more than half of the pelvis

          -  Recovered from prior radiotherapy

          -  No concurrent anticancer radiotherapy

        Surgery:

          -  See Disease Characteristics

        Other:

          -  At least 4 weeks since other prior investigational therapy and recovered

          -  No other concurrent anticancer investigational agents
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Katherine Warren, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00020150

Organization ID

CDR0000067880

Secondary IDs

NCI-00-C-0105I


Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Katherine Warren, MD, Study Chair, National Cancer Institute (NCI)


Verification Date

August 2004