Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00084838 |
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Recruitment Status :
Completed
First Posted : June 11, 2004
Results First Posted : December 24, 2015
Last Update Posted : December 24, 2015
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RATIONALE: Drugs used in chemotherapy work in 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. Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Central Nervous System Tumor, Pediatric | Biological: filgrastim Drug: cisplatin Drug: cyclophosphamide Drug: cytarabine Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: methotrexate Drug: temozolomide Drug: therapeutic hydrocortisone Drug: vincristine sulfate Radiation: radiation therapy Drug: Dactinomycin | Phase 2 |
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 25 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Study of Intrathecal and Systemic Chemotherapy With Radiation Therapy for Children With Central Nervous System Atypical Teratoid/Rhabdoid Tumor (AT/RT) Tumor |
| Study Start Date : | February 2003 |
| Actual Primary Completion Date : | February 2008 |
| Actual Study Completion Date : | March 2013 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. |
Biological: filgrastim
Other Names:
Drug: cisplatin Other Names:
Drug: cyclophosphamide Other Names:
Drug: cytarabine Other Names:
Drug: dexrazoxane hydrochloride Other Names:
Drug: doxorubicin hydrochloride Other Names:
Drug: etoposide Other Name: VP-16 Drug: leucovorin calcium Other Names:
Drug: methotrexate Drug: temozolomide Other Name: Temodar, Methazolastone, Temodal, TMZ, CCRG-81045 Drug: therapeutic hydrocortisone Drug: vincristine sulfate Other Names:
Radiation: radiation therapy Drug: Dactinomycin Other Names:
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- 2-yr Overall Survival [ Time Frame: Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months. ]Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
- Pre-Radiation Therapy Chemotherapeutic Response [ Time Frame: Assessed at study entry and pre-RT/post-CT at week 7. ]
Response pre-RT/post-CT was defined as follows with overall response defined as achieving PR or CR.
Complete Response (CR): Complete resolution of all initially demonstrable tumor on MRI or CT evaluation w/o appearance of any new areas of disease; negative CSF cytology. Partial Response (PR): >/= 50% decrease in the sum of the products of the maximum perpendicular diameters of the tumor (sum LD) relative to baseline w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Stable Disease (SD): <50% decrease in the sum LD w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Progressive Disease (PD): >/= 25% increase in the sum LD relative to baseline, or the appearance of any new areas of disease or appearance of positive cytology after two consecutive negative samples.
- Grade 3/4 Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Auditory/Hearing Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Auditory/Hearing events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Blood/Bone Marrow Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]
All Grade 3-4 Blood/Bone Marrow events based on CTCAEv2 as reported on case report forms.
Arm Name
- Grade 3-4 Gastrointestinal Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Gastrointestinal events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Metabolic/Laboratory Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Metabolic/Laboratory events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Infection/Febrile Neutropenia Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Infection/Febrile Neutropenia events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Neurology Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Neurology events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Pain Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Pain events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Constitutional Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Constitutional events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Muscloskeletal Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Muscloskeletal events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Hepatic Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Hepatic events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Cardiovascular Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Cardiovascular events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Pulmonary Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Pulmonary events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Renal/Genitourinary Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Renal/Genitourinary events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Dermatology Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Dermatology events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Hemorrhage Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Hemorrhage events based on CTCAEv2 as reported on case report forms.
- Grade 3-4 Allergy/Immunology [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ]All Grade 3-4 Allergy/Immunology events based on CTCAEv2 as reported on case report forms.
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
- Histologically confirmed primary intracranial Central Nervous System (CNS) atypical teratoid/rhabdoid tumor OR
- Tumor tissue that possesses the INI-1 gene mutation
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No metastases that disseminate outside the CNS by abdominal and chest computer tomography (CT) scans, kidney imaging, and bone marrow biopsy
- No obstruction of cerebrospinal fluid (CSF) flow by CSF flow study
- Definitive surgical resection of tumor within the past 35 days
PATIENT CHARACTERISTICS:
Age
- 18 and under
Performance status
- Karnofsky 50-100% OR
- Lansky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Hemoglobin > 10 g/dL
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- SGPT < 10 times normal
Renal
- Creatinine ≤ 1.5 times normal
Other
- Willing to have placement of central venous access line
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Prior steroids allowed
Radiotherapy
- No prior radiotherapy
Surgery
- See Disease Characteristics
Other
- No other prior or concurrent investigational agents
- Concurrent anticonvulsant agents allowed
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): NCT00084838
| United States, California | |
| Stanford Cancer Center | |
| Stanford, California, United States, 94305-5826 | |
| United States, Connecticut | |
| Yale Cancer Center | |
| New Haven, Connecticut, United States, 06520-8028 | |
| United States, Georgia | |
| AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus | |
| Atlanta, Georgia, United States, 30342 | |
| United States, Illinois | |
| Children's Memorial Hospital - Chicago | |
| Chicago, Illinois, United States, 60614 | |
| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | |
| Baltimore, Maryland, United States, 21231-2410 | |
| United States, Massachusetts | |
| Children's Hospital Boston | |
| Boston, Massachusetts, United States, 02115 | |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | |
| Boston, Massachusetts, United States, 02115 | |
| United States, Minnesota | |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | |
| Minneapolis, Minnesota, United States, 55404 | |
| United States, Nevada | |
| Sunrise Hospital and Medical Center | |
| Las Vegas, Nevada, United States, 89109 | |
| United States, Ohio | |
| Cleveland Clinic Taussig Cancer Center | |
| Cleveland, Ohio, United States, 44195 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Texas | |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | |
| Dallas, Texas, United States, 75390 | |
| Principal Investigator: | Mark W. Kieran, MD, PhD | Dana-Farber Cancer Institute |
| Responsible Party: | Mark W. Kieran, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00084838 |
| Other Study ID Numbers: |
02-294 DFCI P30CA006516 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 11, 2004 Key Record Dates |
| Results First Posted: | December 24, 2015 |
| Last Update Posted: | December 24, 2015 |
| Last Verified: | December 2015 |
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childhood atypical teratoid/rhabdoid tumor |
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Nervous System Neoplasms Central Nervous System Neoplasms Rhabdoid Tumor Neoplasms by Site Neoplasms Nervous System Diseases Neoplasms, Complex and Mixed Neoplasms by Histologic Type Calcium, Dietary Leucovorin Cytarabine Dactinomycin Hydrocortisone Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate |
Hydrocortisone hemisuccinate Cyclophosphamide Temozolomide Cisplatin Doxorubicin Liposomal doxorubicin Methotrexate Etoposide Vincristine Dexrazoxane Razoxane Lenograstim Calcium Levoleucovorin Immunosuppressive Agents |