Trial Outcomes & Findings for 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 (NCT NCT00047320)
NCT ID: NCT00047320
Last Updated: 2018-02-14
Results Overview
A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
104 participants
Primary outcome timeframe
18 weeks
Results posted on
2018-02-14
Participant Flow
Participant milestones
| Measure |
Radiation Therapy (CR From Induction)
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
radiation therapy: craniospinal irradiation
|
|---|---|
|
Overall Study
STARTED
|
104
|
|
Overall Study
COMPLETED
|
76
|
|
Overall Study
NOT COMPLETED
|
28
|
Reasons for withdrawal
| Measure |
Radiation Therapy (CR From Induction)
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
radiation therapy: craniospinal irradiation
|
|---|---|
|
Overall Study
Lack of Efficacy
|
8
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
8
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Ineligible
|
2
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Radiation Therapy (CR From Induction)
n=104 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
radiation therapy: craniospinal irradiation
|
|---|---|
|
Age, Continuous
|
12 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
72 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
17 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
85 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
88 participants
n=93 Participants
|
|
Region of Enrollment
Canada
|
10 participants
n=93 Participants
|
|
Region of Enrollment
Australia
|
5 participants
n=93 Participants
|
|
Region of Enrollment
New Zealand
|
1 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 18 weeksPopulation: Of the 102 eligible patients, 85 completed induction chemotherapy with sufficient data to assess response. Central review response assessment is used.
A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=85 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
Response to Induction Chemotherapy
Responder
|
74 Participants
|
|
Response to Induction Chemotherapy
Non-Responder
|
11 Participants
|
SECONDARY outcome
Timeframe: At 3 years from study entryPopulation: Two ineligible patients were excluded. A total of 102 eligible patients were analyzed.
Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=102 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
The Probability of Event-free Survival (EFS)
|
0.837 Probability
Interval 0.763 to 0.91
|
SECONDARY outcome
Timeframe: At 3 years from study entryPopulation: Two ineligible patients were excluded. A total of 102 eligible patients were analyzed. one patient died without the disease progression reported. But the death was due to the disease. The death was counted as "event" when progression-free survival (PFS) was calculated. So EFS and PFS at 3 years were same.
Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=102 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
Progression-free Survival (PFS)
|
0.837 Probability
Interval 0.763 to 0.91
|
SECONDARY outcome
Timeframe: At 3 years from study entryPopulation: Two ineligible patients were excluded. A total of 102 eligible patients were analyzed.
Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=102 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
Overall Survival (OS)
|
0.927 Probability
Interval 0.876 to 0.979
|
SECONDARY outcome
Timeframe: During chemotherapy (up to 18 weeks)Population: A total of 102 eligible patients treated with induction chemotherapy were included.
Toxic death, defined as death predominantly attributable to treatment-related causes.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=102 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
Number of Patients Experiencing Toxic Death
|
0 Participants
|
SECONDARY outcome
Timeframe: During chemotherapy(up to 18 weeks)Population: A total of 102 eligible patients treated with induction chemotherapy were included.
The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.
Outcome measures
| Measure |
Radiation Therapy (CR From Induction)
n=102 Participants
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
thiotepa: Given IV
adjuvant therapy
conventional surgery
neoadjuvant therapy
peripheral blood stem cell transplantation
radiation therapy: craniospinal irradiation
|
|---|---|
|
Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
|
22 participants
Interval 14.0 to 31.0
|
Adverse Events
Radiation Therapy (CR From Induction)
Serious events: 8 serious events
Other events: 70 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Radiation Therapy (CR From Induction)
n=102 participants at risk
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
radiation therapy: craniospinal irradiation
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Gastrointestinal disorders
Nausea
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Lymphocyte count decreased
|
0.98%
1/102 • Number of events 2
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Neutrophil count decreased
|
2.9%
3/102 • Number of events 5
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Platelet count decreased
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
White blood cell decreased
|
0.98%
1/102 • Number of events 2
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypernatremia
|
0.98%
1/102 • Number of events 3
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.0%
2/102 • Number of events 3
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Nervous system disorders
Headache
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Nervous system disorders
Seizure
|
0.98%
1/102 • Number of events 1
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
Other adverse events
| Measure |
Radiation Therapy (CR From Induction)
n=102 participants at risk
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
carboplatin: Given IV
etoposide: Given IV
ifosfamide: Given IV
radiation therapy: craniospinal irradiation
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
51/102 • Number of events 108
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.8%
8/102 • Number of events 9
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Gastrointestinal disorders
Nausea
|
7.8%
8/102 • Number of events 16
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Gastrointestinal disorders
Vomiting
|
14.7%
15/102 • Number of events 28
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Infections and infestations
Infections and infestations - Other, specify
|
7.8%
8/102 • Number of events 10
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Alanine aminotransferase increased
|
22.5%
23/102 • Number of events 39
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Aspartate aminotransferase increased
|
14.7%
15/102 • Number of events 22
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Lymphocyte count decreased
|
18.6%
19/102 • Number of events 42
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Neutrophil count decreased
|
52.0%
53/102 • Number of events 104
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
Platelet count decreased
|
52.0%
53/102 • Number of events 96
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Investigations
White blood cell decreased
|
47.1%
48/102 • Number of events 114
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
17.6%
18/102 • Number of events 37
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.8%
8/102 • Number of events 8
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
9.8%
10/102 • Number of events 11
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypernatremia
|
19.6%
20/102 • Number of events 32
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
5.9%
6/102 • Number of events 7
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
14.7%
15/102 • Number of events 22
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.5%
26/102 • Number of events 39
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
8.8%
9/102 • Number of events 13
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
30.4%
31/102 • Number of events 57
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
7.8%
8/102 • Number of events 12
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
|
Nervous system disorders
Headache
|
7.8%
8/102 • Number of events 8
104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
|
Additional Information
Results Reporting Coordinator
Children's Oncology Group
Phone: 352-273-0558
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
- Publication restrictions are in place
Restriction type: OTHER