Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
Study Details
Study Description
Brief Summary
This phase II trial studies how well combination chemotherapy works in treating younger patients with newly diagnosed, non-metastatic desmoplastic medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cyclophosphamide, methotrexate, etoposide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- Estimate of the progression free survival (PFS) distribution for patients 0-<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
OTHER PRE-SPECIFIED OBJECTIVES:
-
Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.
-
Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma with extensive nodularity (MBEN) medulloblastoma in young children.
-
Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.
OUTLINE:
INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36, 48, 60, and 72 months.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (combination chemotherapy) INDUCTION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity. CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity. |
Drug: Carboplatin
Given IV
Other Names:
Other: Cognitive Assessment
Optional ancillary studies
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Methotrexate
Given IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) [2 years from diagnosis]
Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
- Overall Survival (OS) [Assessed up to 72 months, reported at 2 years from diagnosis]
Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months.
- Event-free Survival (EFS) [2 years from diagnosis]
Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
- Percentage of Patients With Responses at 189 Days [189 days from start of treatment]
The percentage of patients with complete response (CR) at the end of induction (~189 days) was reported and presented with the associated exact 95% confidence interval.
- Percentage of Patients With Responses at 273 Days [273 days from start of treatment]
The percentage of patients with complete response (CR) at the end of therapy (~273 days) was reported and presented with the associated exact 95% confidence interval.
Other Outcome Measures
- Feasibility of Rapid Central Pathology Screening Review Defined as Success Rate of Timely Central Pathology Review Based on the Expectation That at Least 95% of the Cases Will be Reviewed Within 10 Days [Up to 10 days]
At the end of the trial the feasibility of such a prescreening process will be assessed by reporting the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides.
- Molecular Profile [Up to 2 years]
Contingency table analysis will be used to examine the association of molecular profile with histology.
- Change in Neurocognitive and Adaptive Functioning Assessed Using Full Scale IQ Score (FSIQ) and General Adaptive Composite Score (GAC) [Baseline to up to 60 months]
Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
-
Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
-
Patients must have:
-
Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
-
Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
-
Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery
-
Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
-
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =< 16 years of age
-
Patients must have a life expectancy of >= 8 weeks
-
Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
-
Peripheral absolute neutrophil count (ANC) >= 1000/uL
-
Platelet count >= 100,000/uL (transfusion independent)
-
Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
-
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
-
1 month to < 6 months: 0.4 mg/dL
-
6 months to < 1 year: 0.5 mg/dL
-
1 to < 2 years: 0.6 mg/dL
-
2 to < 6 years: 0.8 mg/dL
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
-
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age
-
Central nervous system function defined as:
-
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
-
Patients must not be in status, coma or assisted ventilation prior to study enrollment
Exclusion Criteria:
-
Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible
-
Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
2 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
3 | The University of Arizona Medical Center-University Campus | Tucson | Arizona | United States | 85724 |
4 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
5 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
6 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
7 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
8 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
9 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
10 | Valley Children's Hospital | Madera | California | United States | 93636 |
11 | Children's Hospital and Research Center at Oakland | Oakland | California | United States | 94609-1809 |
12 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
13 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
14 | Sutter Medical Center Sacramento | Sacramento | California | United States | 95816 |
15 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
16 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
17 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
18 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
19 | Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center | Torrance | California | United States | 90502 |
20 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
21 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
22 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
23 | Yale University | New Haven | Connecticut | United States | 06520 |
24 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
25 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
26 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
27 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
28 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
29 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
30 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
31 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
32 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
33 | Florida Hospital Orlando | Orlando | Florida | United States | 32803 |
34 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
35 | UF Cancer Center at Orlando Health | Orlando | Florida | United States | 32806 |
36 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
37 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
38 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
39 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
40 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
41 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
42 | Augusta University Medical Center | Augusta | Georgia | United States | 30912 |
43 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
44 | Saint Luke's Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
45 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
46 | University of Illinois | Chicago | Illinois | United States | 60612 |
47 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
48 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
49 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
50 | Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | United States | 60068 |
51 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61637 |
52 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
53 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
54 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
55 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
56 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
57 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
58 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
59 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
60 | Ochsner Medical Center Jefferson | New Orleans | Louisiana | United States | 70121 |
61 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
62 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
63 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
64 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
65 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889-5600 |
66 | University of Massachusetts Medical School | Worcester | Massachusetts | United States | 01655 |
67 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
68 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
69 | Ascension Saint John Hospital | Detroit | Michigan | United States | 48236 |
70 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
71 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
72 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
73 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
74 | Beaumont Children's Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
75 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
76 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
77 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
78 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
79 | Columbia Regional | Columbia | Missouri | United States | 65201 |
80 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
81 | Cardinal Glennon Children's Medical Center | Saint Louis | Missouri | United States | 63104 |
82 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
83 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
84 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
85 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
86 | Sunrise Hospital and Medical Center | Las Vegas | Nevada | United States | 89109 |
87 | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | United States | 89135 |
88 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
89 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
90 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
91 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
92 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
93 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
94 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
95 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87102 |
96 | Albany Medical Center | Albany | New York | United States | 12208 |
97 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
98 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
99 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
100 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
101 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
102 | Mount Sinai Hospital | New York | New York | United States | 10029 |
103 | Columbia University/Herbert Irving Cancer Center | New York | New York | United States | 10032 |
104 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
105 | University of Rochester | Rochester | New York | United States | 14642 |
106 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
107 | New York Medical College | Valhalla | New York | United States | 10595 |
108 | Mission Hospital Inc-Memorial Campus | Asheville | North Carolina | United States | 28801 |
109 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
110 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
111 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
112 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
113 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
114 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
115 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
116 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
117 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
118 | The Toledo Hospital/Toledo Children's Hospital | Toledo | Ohio | United States | 43606 |
119 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
120 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
121 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
122 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
123 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
124 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
125 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
126 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
127 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
128 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
129 | Palmetto Health Richland | Columbia | South Carolina | United States | 29203 |
130 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
131 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
132 | T C Thompson Children's Hospital | Chattanooga | Tennessee | United States | 37403 |
133 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
134 | St. Jude Children's Research Hospital | Memphis | Tennessee | United States | 38105 |
135 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
136 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
137 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
138 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
139 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
140 | El Paso Children's Hospital | El Paso | Texas | United States | 79905 |
141 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
142 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
143 | Children's Hospital of San Antonio | San Antonio | Texas | United States | 78207 |
144 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
145 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
146 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
147 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
148 | University of Vermont College of Medicine | Burlington | Vermont | United States | 05405 |
149 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
150 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
151 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
152 | Carilion Clinic Children's Hospital | Roanoke | Virginia | United States | 24014 |
153 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
154 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
155 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
156 | West Virginia University Healthcare | Morgantown | West Virginia | United States | 26506 |
157 | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | United States | 54449 |
158 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
159 | John Hunter Children's Hospital | Hunter Regional Mail Centre | New South Wales | Australia | 2310 |
160 | Women's and Children's Hospital-Adelaide | North Adelaide | South Australia | Australia | 5006 |
161 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
162 | Alberta Children's Hospital | Calgary | Alberta | Canada | T3B 6A8 |
163 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | V6H 3V4 |
164 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
165 | Janeway Child Health Centre | Saint John's | Newfoundland and Labrador | Canada | A1B 3V6 |
166 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
167 | McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8N 3Z5 |
168 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
169 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
170 | Centre Hospitalier Universitaire Sainte-Justine | Montreal | Quebec | Canada | H3T 1C5 |
171 | Centre Hospitalier Universitaire de Quebec | Quebec | Canada | G1V 4G2 | |
172 | San Jorge Children's Hospital | San Juan | Puerto Rico | 00912 | |
173 | University Pediatric Hospital | San Juan | Puerto Rico | 00926 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Lucie E Lafay-Cousin, Children's Oncology Group
Study Documents (Full-Text)
More Information
Publications
None provided.- ACNS1221
- NCI-2013-02379
- ACNS1221
- COG-ACNS1221
- s15-00476
- ACNS1221
- ACNS1221
- U10CA180886
- U10CA098543
Study Results
Participant Flow
Recruitment Details | This study opened for entry on December 24, 2013, and the first patient was enrolled on April 22, 2014. The study enrolled 26 patients before being closed early due to inferior efficacy as of July 27, 2016. 25 of the 26 patients enrolled were deemed to be eligible |
---|---|
Pre-assignment Detail |
Arm/Group Title | All Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All patients enrolled on the study. Patients received 3-5 cycles of therapy which included cyclophosphamide (800 mg/m2/day), vincristine (1.5 mg/m2/day), methotrexate (5,000 mg/m2), etoposide (150 mg/m2/dose) and carboplatin (200 mg/m2/day IV). |
Period Title: Overall Study | |
STARTED | 26 |
COMPLETED | 25 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Overall Participants | 26 |
Age (Count of Participants) | |
<=18 years |
26
100%
|
Between 18 and 65 years |
0
0%
|
>=65 years |
0
0%
|
Age (months (at time of dx)) [Median (Full Range) ] | |
Median (Full Range) [months (at time of dx)] |
19.7
|
Sex: Female, Male (Count of Participants) | |
Female |
10
38.5%
|
Male |
16
61.5%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
6
23.1%
|
Not Hispanic or Latino |
19
73.1%
|
Unknown or Not Reported |
1
3.8%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
3.8%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
2
7.7%
|
White |
20
76.9%
|
More than one race |
0
0%
|
Unknown or Not Reported |
3
11.5%
|
Region of Enrollment (participants) [Number] | |
United States |
23
88.5%
|
Canada |
3
11.5%
|
Outcome Measures
Title | Progression-free Survival (PFS) |
---|---|
Description | Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's. |
Time Frame | 2 years from diagnosis |
Outcome Measure Data
Analysis Population Description |
---|
26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses. |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Measure Participants | 25 |
Number (95% Confidence Interval) [percent probability] |
52.0
|
Title | Overall Survival (OS) |
---|---|
Description | Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months. |
Time Frame | Assessed up to 72 months, reported at 2 years from diagnosis |
Outcome Measure Data
Analysis Population Description |
---|
26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses. |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Measure Participants | 25 |
Number (95% Confidence Interval) [percent probability] |
92.0
|
Title | Event-free Survival (EFS) |
---|---|
Description | Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's. |
Time Frame | 2 years from diagnosis |
Outcome Measure Data
Analysis Population Description |
---|
26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient is excluded from all analyses. |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Measure Participants | 25 |
Number (95% Confidence Interval) [percent probability] |
52.0
|
Title | Percentage of Patients With Responses at 189 Days |
---|---|
Description | The percentage of patients with complete response (CR) at the end of induction (~189 days) was reported and presented with the associated exact 95% confidence interval. |
Time Frame | 189 days from start of treatment |
Outcome Measure Data
Analysis Population Description |
---|
26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient was excluded from all analyses. |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Measure Participants | 25 |
Number (95% Confidence Interval) [Percentage of patients] |
92.0
|
Title | Percentage of Patients With Responses at 273 Days |
---|---|
Description | The percentage of patients with complete response (CR) at the end of therapy (~273 days) was reported and presented with the associated exact 95% confidence interval. |
Time Frame | 273 days from start of treatment |
Outcome Measure Data
Analysis Population Description |
---|
26 patients were enrolled on the protocol, but 1 was deemed ineligible. The ineligible patient is excluded from all analyses. |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) |
---|---|
Arm/Group Description | All eligible patients enrolled on the study |
Measure Participants | 25 |
Number (95% Confidence Interval) [Percentage of patients] |
88.0
|
Title | Feasibility of Rapid Central Pathology Screening Review Defined as Success Rate of Timely Central Pathology Review Based on the Expectation That at Least 95% of the Cases Will be Reviewed Within 10 Days |
---|---|
Description | At the end of the trial the feasibility of such a prescreening process will be assessed by reporting the percentage and the associated confidence interval of cases where the central review was obtained within 10 days from receipt of slides. |
Time Frame | Up to 10 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Molecular Profile |
---|---|
Description | Contingency table analysis will be used to examine the association of molecular profile with histology. |
Time Frame | Up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Change in Neurocognitive and Adaptive Functioning Assessed Using Full Scale IQ Score (FSIQ) and General Adaptive Composite Score (GAC) |
---|---|
Description | Changes will be described via paired tests and confidence intervals both for FSIQ and GAC in order to capture any deterioration over time. |
Time Frame | Baseline to up to 60 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | 1 year | |
---|---|---|
Adverse Event Reporting Description | Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events. | |
Arm/Group Title | All Eligible Patients (Combination Chemotherapy) | |
Arm/Group Description | All eligible patients enrolled on the study | |
All Cause Mortality |
||
All Eligible Patients (Combination Chemotherapy) | ||
Affected / at Risk (%) | # Events | |
Total | 2/25 (8%) | |
Serious Adverse Events |
||
All Eligible Patients (Combination Chemotherapy) | ||
Affected / at Risk (%) | # Events | |
Total | 2/25 (8%) | |
General disorders | ||
Death NOS | 1/25 (4%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Other, Progression Of Medulloblastoma | 1/25 (4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
All Eligible Patients (Combination Chemotherapy) | ||
Affected / at Risk (%) | # Events | |
Total | 17/25 (68%) | |
Blood and lymphatic system disorders | ||
Febrile neutropenia | 1/25 (4%) | 1 |
Leukocytosis | 1/25 (4%) | 4 |
Ear and labyrinth disorders | ||
Hearing impaired | 1/25 (4%) | 1 |
Infections and infestations | ||
Meningitis | 1/25 (4%) | 1 |
Investigations | ||
Lymphocyte count decreased | 7/25 (28%) | 18 |
Neutrophil count decreased | 14/25 (56%) | 36 |
Platelet count decreased | 7/25 (28%) | 13 |
White blood cell decreased | 11/25 (44%) | 24 |
Metabolism and nutrition disorders | ||
Hypernatremia | 1/25 (4%) | 1 |
Hypokalemia | 1/25 (4%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Must obtain prior Sponsor approval
Results Point of Contact
Name/Title | Results Reporting Coordinator |
---|---|
Organization | Children's Oncology Group |
Phone | 626-446-0064 |
resultsreportingcoordinator@childrensoncologygroup.org |
- ACNS1221
- NCI-2013-02379
- ACNS1221
- COG-ACNS1221
- s15-00476
- ACNS1221
- ACNS1221
- U10CA180886
- U10CA098543