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Trial record 34 of 42 for:    Malignant Hyperthermia 5

Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor

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ClinicalTrials.gov Identifier: NCT00085098
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : November 6, 2013
Last Update Posted : September 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Brain Tumor
Central Nervous System Tumor
Interventions Biological: filgrastim
Drug: carboplatin
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Radiation: radiation therapy
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks. Courses 1,2:Patients (PTS) receive carboplatin IV over 1 hour on days 1-2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, PTS with complete response (CR) undergo low-dose radiation therapy 5 days a week for 5 weeks. PTS with minimal residual disease (MRD), a PR, or stable disease (SD) receive chemotherapy courses 3,4. Courses 3,4:PTS receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2-3 and filgrastim (G-CSF) subcutaneous (SC) or IV on day 4 continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. PTS achieving a CR or MRD proceed to reduced-dose radiotherapy. PTS with a partial response (PR), SD or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A.Reduced-dose radiation therapy: Within 6 weeks of starting course 4, PTS undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks.
Period Title: Overall Study
Started 11 13
Completed 10 11
Not Completed 1 2
Reason Not Completed
Withdrawal by Subject             0             1
Ineligible             1             1
Arm/Group Title Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy) Total
Hide Arm/Group Description Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A.

Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Total of all reporting groups
Overall Number of Baseline Participants 11 13 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 13 participants 24 participants
<=18 years
10
  90.9%
13
 100.0%
23
  95.8%
Between 18 and 65 years
1
   9.1%
0
   0.0%
1
   4.2%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 13 participants 24 participants
Female
4
  36.4%
1
   7.7%
5
  20.8%
Male
7
  63.6%
12
  92.3%
19
  79.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 13 participants 24 participants
United States 10 8 18
Australia 1 4 5
Switzerland 0 1 1
1.Primary Outcome
Title Event-free Survival
Hide Description

Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.

QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.

Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol’s primary objective.

NOTE: Reported data are through May 2009 (see Caveats section).

Time Frame Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
By protocol design, all eligible patients were considered in the evaluation of primary study aim. Two (2) patients were considered ineligible. All other patients (10 enrolled to regimen A and 12 enrolled to regimen B) are included in the evaluation for the primary outcome measure.
Arm/Group Title Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description:
Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A.

Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Overall Number of Participants Analyzed 10 12
Measure Type: Number
Unit of Measure: participants
Experienced a qualifying event 1 1
Event-free through 3 years of follow-up 0 0
Event-free at data cutoff (if < 3 years follow-up) 9 11
Withdrew from study prior to 3 years of follow-up 0 0
Lost to follow-up prior to 3 years of follow-up 0 0
2.Secondary Outcome
Title Number of Participants With a Response to Regimen B
Hide Description To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions.
Time Frame 5 years from beginning of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were treated in Regimen B and had at least one response assessment are included in this analysis. One patient in Regimen B withdrew from the pre-Radiotherapy chemotherapy and did not have any response assessment were not included for the response analysis.
Arm/Group Title Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description:

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A.

Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks.

Overall Number of Participants Analyzed 11
Measure Type: Count of Participants
Unit of Measure: Participants
8
  72.7%
3.Secondary Outcome
Title Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Hide Description The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. The list of toxicities of interest include Anemia or Febrile Neutropenia; Nausea or Vomiting; Infections and Infestations; Neutrophil or White blood count decrease; and Hypokalemia or Hyponatremia
Time Frame From the beginning of treatment, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received any pre-radiotherapy chemotherapy in Regimen B
Arm/Group Title Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description:

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF), subcutaneous (SC) or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia or Febrile Neutropenia
2
  16.7%
Nausea or Vomiting
2
  16.7%
Infections and Infestations
2
  16.7%
Neutorphil or White blood count decrease
7
  58.3%
Hypokalemia or Hyponatremia
3
  25.0%
4.Secondary Outcome
Title Quality of Life (QOL) and Neurocognitive Assessment (NP)
Hide Description The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. The scores range from 0 to 100 with higher score reflecting better QoL or neurocognitive assessment.
Time Frame 2 years from beginning of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who also successfully completed therapy and were assessed for quality of life and neurocognitive outcome.
Arm/Group Title Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description:

Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

radiation therapy: Patients undergo radiotherapy 5 days a week

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A.

Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Overall Number of Participants Analyzed 10 11
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Overall IQ Score Number Analyzed 5 participants 7 participants
98.60  (17.95) 92.43  (6.27)
Self Report Score-Internalizing Problems Number Analyzed 2 participants 4 participants
41.00  (2.83) 42.50  (5.51)
Self Report Score-Emotional Problems Number Analyzed 2 participants 4 participants
44.00  (2.83) 42.00  (4.55)
Self Report Score-Personal Adjustment Strengths Number Analyzed 2 participants 4 participants
51.50  (2.12) 60.50  (3.32)
Parent Report QoL Total Score Number Analyzed 2 participants 2 participants
88.04  (6.15) 79.35  (6.15)
Self Report QoL Total Score Number Analyzed 1 participants 2 participants
95.65 [1]   (NA) 90.76  (0.76)
[1]
The Reg A only has 1 pt with Self Report QoL Total Score, so the Standard Deviation cannot be estimated.
Time Frame During protocol therapy; six months (maximum).
Adverse Event Reporting Description

All eligible patients were considered in the evaluation of adverse events (AEs). Two patients were considered ineligible. All other patients (10 enrolled to regimen A and 12 enrolled to regimen B) are included in AE reporting.

Systematic assessment was performed according to protocol-directed schedule of assessments, and as clinically indicated.

 
Arm/Group Title Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Hide Arm/Group Description Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A.

Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

All-Cause Mortality
Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen A (Radiotherapy Only) Regimen B (Chemotherapy Plus Radiotherapy)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/10 (40.00%)      11/12 (91.67%)    
Blood and lymphatic system disorders     
Anemia   0/10 (0.00%)  0 2/12 (16.67%)  2
Febrile neutropenia   0/10 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders     
Nausea   1/10 (10.00%)  1 1/12 (8.33%)  1
Vomiting   1/10 (10.00%)  1 2/12 (16.67%)  2
General disorders     
Fatigue   1/10 (10.00%)  1 1/12 (8.33%)  1
Immune system disorders     
Anaphylaxis   0/10 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
"Infections and infestations - Other, specify"   0/10 (0.00%)  0 2/12 (16.67%)  2
Investigations     
Alanine aminotransferase increased   0/10 (0.00%)  0 2/12 (16.67%)  2
GGT increased   0/10 (0.00%)  0 1/12 (8.33%)  1
Lymphocyte count decreased   3/10 (30.00%)  3 4/12 (33.33%)  4
Neutrophil count decreased   0/10 (0.00%)  0 9/12 (75.00%)  9
Platelet count decreased   0/10 (0.00%)  0 7/12 (58.33%)  7
White blood cell decreased   1/10 (10.00%)  1 5/12 (41.67%)  5
Metabolism and nutrition disorders     
Anorexia   1/10 (10.00%)  1 0/12 (0.00%)  0
Dehydration   1/10 (10.00%)  1 0/12 (0.00%)  0
Hyperglycemia   1/10 (10.00%)  1 1/12 (8.33%)  1
Hypernatremia   1/10 (10.00%)  1 1/12 (8.33%)  1
Hypokalemia   1/10 (10.00%)  1 2/12 (16.67%)  2
Hyponatremia   0/10 (0.00%)  0 3/12 (25.00%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
"Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify"   0/10 (0.00%)  0 1/12 (8.33%)  1
Nervous system disorders     
Peripheral motor neuropathy   1/10 (10.00%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
Study closed early due to slow accrual. Analysis plans were not carried out (lack of statistical precision compromised the ability to draw appropriate conclusions). Reported Primary Outcome Measure data reflects data collection through May 2009.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Coordinator
Organization: Children's Oncology Group
Phone: (626) 447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00085098     History of Changes
Other Study ID Numbers: ACNS0232
CDR0000367294 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0232 ( Other Identifier: Children's Oncology Group )
First Submitted: June 10, 2004
First Posted: June 11, 2004
Results First Submitted: June 7, 2013
Results First Posted: November 6, 2013
Last Update Posted: September 7, 2018