Trial Outcomes & Findings for Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma (NCT NCT00031590)

Last Updated: 2019-04-25

Results Overview

Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

3 years

Results posted on

2019-04-25

Participant Flow

Subjects were enrolled at three participating institutions namely Childrens Hospital of Philadelphia, Stanford University and Emory University.

Thirty subjects signed consent. One subject was deemed ineligible due to positive cerebrospinal fluid (CSF) and second subject was declared ineligible due to delayed start of radiation therapy (RT). Remaining 28 subjects continued on study.

Participant milestones

Participant milestones
Measure	Study Treatment All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B. Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6
Overall Study STARTED	28
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Study Treatment All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B. Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6
Overall Study Adverse Event	1
Overall Study Withdrawal by parents	2

Baseline Characteristics

Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Treatment n=28 Participants All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B. Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6
Age, Categorical <=18 years	28 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race/Ethnicity, Customized White	17 participants n=5 Participants
Race/Ethnicity, Customized African american	5 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	5 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 years

Population: The primary endpoint was not met due to lack of evaluable data from non-compliance with neurocognitive testing. Baseline neurocognitive testing was performed on 5 of 28 (18%) of study subjects. Of those 5 subjects with baseline testing, only 1 completed follow up neurocognitive testing at the protocol specified time points.

Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.

Population: All subjects who received radiation and started chemotherapy.

Survival Endpoints: Event free survival and overall survival were assessed at 5 years from time of study enrollment

Outcome measures

Outcome measures
Measure	Study Treatment n=28 Participants All subjects will undergo surgical resection and routine staging (MRI spine and LP for CSF cytology). Subjects aged 3-30 yrs with M0 disease are eligible. Treatment must begin within 28 days of surgery. Reduced dose craniospinal irradiation (CSI) (1800 centiGray (cGy) CSI + 3780 cGy tumor bed) will last for 6 weeks with concurrent, weekly vincristine. 4 weeks after radiation therapy is completed, all subjects will begin 9 cycles of maintenance chemotherapy: Regimen A (CCNU, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide). Cycles will be given as AABAABAAB Regimen A: Cisplatin: 70mg/m2/dose x 1 dose on day 0 Vincristine: 1.5 mg/m2/dose on days 0, 7, 14 CCNU: 75 mg/m2/dose x 1 dose on day 0 Regimen B: Cyclophosphamide: 1g/m2/dose on days 0 and 1 Etoposide: 150 mg/m2/dose (IV) on days 0 and 1 Etoposide: 50 mg/m2/day PO on days 14-34 (21 days total)
Long Term Survival 5 year Overall Survival (OS)	87.5 Percentage of participants
Long Term Survival 5 year Event Free Survival (EFS)	70 Percentage of participants

Adverse Events

Study Treatment

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Study Treatment n=28 participants at risk All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6
Ear and labyrinth disorders hearing loss	53.6% 15/28 Adverse events were recorded in the following categories: auditory toxicity, renal toxicity, and endocrinologic toxicity
Renal and urinary disorders creatinine clearance	17.9% 5/28 Adverse events were recorded in the following categories: auditory toxicity, renal toxicity, and endocrinologic toxicity
Endocrine disorders thyroid dysfunction	39.3% 11/28 Adverse events were recorded in the following categories: auditory toxicity, renal toxicity, and endocrinologic toxicity
Endocrine disorders growth hormone deficiency	21.4% 6/28 Adverse events were recorded in the following categories: auditory toxicity, renal toxicity, and endocrinologic toxicity

Additional Information

Peter Phillips

Childrens Hospital of Philadelphia

Phone: 215-590-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place