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| ID | Type | Description | Link |
|---|---|---|---|
| POG-9879 | |||
| CDR0000066706 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients with newly diagnosed brain stem glioma.
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of vincristine given as an IV push dose in combination with continuous infusion cyclosporine and oral etoposide concurrent with and prior to radiotherapy in children with newly diagnosed primary intrinsic brain stem glioma. II. Determine the incidence and severity of other toxicities of vincristine in this regimen in these patients. III. Determine a safe and tolerable dose of vincristine under these conditions to be used in phase II studies. IV. Seek preliminary evidence of antitumor activity in this setting in these patients.
OUTLINE: This is dose escalation study of vincristine. Patients receive radiotherapy daily for 6 weeks with concurrent induction chemotherapy. Induction chemotherapy consists of vincristine IV push weekly for 6 weeks, oral etoposide daily on days 1-21 and 29-49 and cyclosporine IV over 2 hours prior to vincristine followed by a continuous 36 hour infusion. Cohorts of 3-6 patients receive escalating doses of vincristine. If dose limiting toxicity (DLT) occurs in 2 or more of 3-6 patients, the maximum tolerated dose (MTD) has been exceeded and the preceding dose is declared the MTD. Maintenance therapy consists of 6 monthly courses of cyclosporine IV over 36 hours beginning on day 1, vincristine IV push on day 1, and oral etoposide daily for days 1-21. Patients are followed every 6 months for 4 years and then annually thereafter.
PROJECTED ACCRUAL: At least 6 patients will be accrued into this study at a rate of 12 patients per year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stratum 1 | Experimental | Concomitant irradiation and vincristine sulfate in esc dose beginning with 0.8 mg/m2, etoposide and Cyclosporine A given over 6 weeks, then monthly maint courses over 6 mths, with no clinical and radiologic progression. Stable disease indicates continuation of therapy. Clinical deterioration within 4 months of completion of radiation therapy must be confirmed to be PD by imaging. Clinical progression even in the absence of imaging changes will be accepted as reflecting disease progression. Steroids dexamethasone (Decadron) given as clinically indicated and tapered as tolerated. Steroids may decrease capillary permeability to chemotherapeutic agents and antagonise the effect of cyclosporin A. Also contributes to the syndrome of seizures and white matter changes seen with cyclosporine in the post BMT period. If steroid use is required, the recommended schedule of Decadron dosing during the 6 week induction course is 8 mg/m2 divided q 6-8 hours. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cyclosporine | Drug |
|
| |
| etoposide |
| Measure | Description | Time Frame |
|---|---|---|
| Event Free Survival |
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DISEASE CHARACTERISTICS: Newly diagnosed diffuse intrinsic brain stem glioma by MRI Biopsy is neither necessary nor encouraged A least two-thirds of the tumor is in the pons Origin of the tumor is clearly in the pons Must be registered within 28 days of diagnosis Clinical history less than 6 months duration (cranial nerve deficit, long tract signs, or ataxia) No diffuse leptomeningeal disease
PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky or Lansky 50-100% Life expectancy: At least 6 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hepatic: SGPT less than 2 times normal Renal: Creatinine normal for age OR Creatinine clearance greater than 70 mL/min
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: Prior steroids at stable or decreasing doses allowed Radiotherapy: No prior radiotherapy Surgery: Not specified Other: No other concurrent investigational agents
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| Name | Affiliation | Role |
|---|---|---|
| Mark L. Greenberg, MD | The Hospital for Sick Children | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Comprehensive Cancer Center | Birmingham | Alabama | 35294 | United States | ||
| Arizona Cancer Center |
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| Drug |
|
|
| vincristine sulfate | Drug |
|
|
| radiation therapy | Radiation |
|
| Tucson |
| Arizona |
| 85724 |
| United States |
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| University of California San Diego Cancer Center | La Jolla | California | 92093-0658 | United States |
| Lucile Packard Children's Hospital at Stanford | Palo Alto | California | 94304 | United States |
| Sutter Cancer Center | Sacramento | California | 95816 | United States |
| Kaiser Permanente-Southern California Permanente Medical Group | San Diego | California | 92120 | United States |
| Naval Medical Center - San Diego | San Diego | California | 92134-3202 | United States |
| Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | 95051-5386 | United States |
| Nemours Children's Clinic | Jacksonville | Florida | 32207 | United States |
| Sylvester Cancer Center, University of Miami | Miami | Florida | 33136 | United States |
| Baptist Hospital of Miami | Miami | Florida | 33176-2197 | United States |
| Walt Disney Memorial Cancer Institute | Orlando | Florida | 32803 | United States |
| St. Mary's Hospital | West Palm Beach | Florida | 33407 | United States |
| Emory University Hospital - Atlanta | Atlanta | Georgia | 30322 | United States |
| Tripler Army Medical Center | Honolulu | Hawaii | 96859-5000 | United States |
| Rush-Presbyterian-St. Luke's Medical Center | Chicago | Illinois | 60612 | United States |
| Children's Memorial Hospital, Chicago | Chicago | Illinois | 60614 | United States |
| Christ Hospital | Oak Lawn | Illinois | 60453 | United States |
| Saint Jude Midwest Affiliate | Peoria | Illinois | 61602 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160-7357 | United States |
| Via Christi Regional Medical Center-Saint Francis Campus | Wichita | Kansas | 67214 | United States |
| Tulane University School of Medicine | New Orleans | Louisiana | 70112 | United States |
| Eastern Maine Medical Center | Bangor | Maine | 04401 | United States |
| Maine Children's Cancer Program | Portland | Maine | 04101 | United States |
| Johns Hopkins Oncology Center | Baltimore | Maryland | 21287 | United States |
| Floating Hospital for Children | Boston | Massachusetts | 02111 | United States |
| Massachusetts General Hospital Cancer Center | Boston | Massachusetts | 02114 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| St. John's Hospital and Medical Center | Detroit | Michigan | 48236 | United States |
| Hurley Medical Center | Flint | Michigan | 48503 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216-4505 | United States |
| Keesler Medical Center - Keesler AFB | Keesler Air Force Base | Mississippi | 39534-2576 | United States |
| University of Missouri-Columbia Hospital and Clinics | Columbia | Missouri | 65212 | United States |
| Cardinal Glennon Children's Hospital | St Louis | Missouri | 63104 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Norris Cotton Cancer Center | Lebanon | New Hampshire | 03756 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| University of New Mexico School of Medicine | Albuquerque | New Mexico | 87131 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263-0001 | United States |
| State University of New York Health Sciences Center - Stony Brook | Stony Brook | New York | 11790-9832 | United States |
| State University of New York - Upstate Medical University | Syracuse | New York | 13210 | United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| Oklahoma Memorial Hospital | Oklahoma City | Oklahoma | 73126-0307 | United States |
| Natalie Warren Bryant Cancer Center | Tulsa | Oklahoma | 74136 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425-0721 | United States |
| James H. Quillen College of Medicine | Johnson City | Tennessee | 37614-0622 | United States |
| Saint Jude Children's Research Hospital | Memphis | Tennessee | 38105-2794 | United States |
| Medical City Dallas Hospital | Dallas | Texas | 75230 | United States |
| Simmons Cancer Center - Dallas | Dallas | Texas | 75235-9154 | United States |
| Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | 76104 | United States |
| University of Texas Medical Branch | Galveston | Texas | 77555-1329 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| San Antonio Military Pediatric Cancer and Blood Disorders Center | Lackland Air Force Base | Texas | 78236-5300 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78284 | United States |
| Scott and White Clinic | Temple | Texas | 76508 | United States |
| Vermont Cancer Center | Burlington | Vermont | 05401-3498 | United States |
| Inova Fairfax Hospital | Falls Church | Virginia | 22046 | United States |
| Carilion Roanoke Memorial Hospital | Roanoke | Virginia | 24029 | United States |
| Madigan Army Medical Center | Tacoma | Washington | 98431-5000 | United States |
| West Virginia University Medical School, Charleston Division | Charleston | West Virginia | 25304 | United States |
| West Virginia University Hospitals | Morgantown | West Virginia | 26506-9162 | United States |
| St. Vincent Hospital | Green Bay | Wisconsin | 54307-3508 | United States |
| Midwest Children's Cancer Center | Milwaukee | Wisconsin | 53226 | United States |
| Alberta Children's Hospital | Calgary | Alberta | T2T 5C7 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Montreal Children's Hospital | Montreal | Quebec | H3H 1P3 | Canada |
| Hopital Sainte Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Centre Hospitalier de L'Universite Laval | Sainte-Foy | Quebec | GIV 4G2 | Canada |
| Academisch Ziekenhuis Groningen | Groningen | 9713 EZ | Netherlands |
| San Jorge Childrens Hospital | Santurce | 00912 | Puerto Rico |
| Clinique de Pediatrie | Geneva | 1211 | Switzerland |
| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D005047 | Etoposide |
| D014750 | Vincristine |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D013812 | Therapeutics |
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