Ependymoma, Medulloblastoma, Neuroblastoma (Measurable Disease), Neuroblastoma (Metaiodobenzylguanidine, Non-brainstem High-grade Glioma, Osteosarcoma, Positive Evaluable), Rhabdomyosarcoma, Sarcoma, Ewing's
Conditions
Brief summary
To determine the response rate of pemetrexed given every 21 days for the treatment of children with relapsed or refractory osteosarcoma, Ewing's sarcoma/peripheral primitive neuroectodermal tumors (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET or non-brain stem high-grade glioma.
Interventions
DRUGpemetrexed
1910 milligrams per meter squared (mg/m\^2) (or 60 milligrams per kilogram \[mg/kg\] if patient \<12 months old), intravenous (IV), for 21 days x 17 cycles
Sponsors
Children's Oncology Group
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 22 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have osteosarcoma, Ewing's sarcoma, medulloblastoma, neuroblastoma, rhabdomyosarcoma, ependymoma or high-grade non-brainstem glioma * Measurable disease * Eastern Cooperative Oncology Group (ECOG) performance 0,1,2 * Adequate renal, liver and bone marrow function * Patient's current disease state must be one with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Exclusion criteria
* Growth factors that support platelet or white cell number or function must not have been administered within the last 7 days prior to enrollment (14 days if Neulasta) * Patients with central nervous system (CNS) tumors who have not been on a stable or decreasing dose of dexamethasone or other corticosteroid for 7 days prior to enrollment * Patients with uncontrolled infection * Patients who have received pemetrexed previously * Patients with pleural effusions or ascites
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Tumor Response (Response Rate) | baseline to measured progressive disease (up to 1 year) | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response = disappearance of all target lesions. Partial Response = 30% decrease in sum of longest diameter of target lesions. Response rate (percent \[%\])= (number of participants with complete response (CR) or partial response (PR) in stratum/number of participants in stratum)\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | every cycle (up to 2 years and 7 months) | AdEERS= Adverse Event Expedited Reporting System; AE = adverse event. Patients may be counted in more than 1 category. Includes events that were considered possibly related to study drug (PRSD) as judged by the investigator. |
| Pharmacogenomics - Measure the Response of Genes Related to Toxicity | baseline | The pharmacogenomics outcomes examining the correlation between the presence of the methylene tetrahydrofolate reductase gene and the presence of a polymorphism in the thymidylate synthase (TS) gene and/or gene promoter and toxicity were optional and will not be reported here. Results of this optional research may be reported in the future by the Children's Oncology Group in the peer-reviewed literature. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Osteosarcoma Pemetrexed 1910 milligrams per meters squared (mg/m\^2) (or 60 milligrams per kilogram \[mg/kg\] if patient \<12 months old) | 10 |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 11 |
| Rhabdomyosarcoma Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 9 |
| Neuroblastoma (Measureable Disease) Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 5 |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 6 |
| Ependymoma Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 10 |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 11 |
| Non-Brainstem High-Grade Glioma Pemetrexed 1910 mg/m\^2 (or 60 mg/kg if patient \<12 months old) | 10 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Toxicity Requiring Removal from Study | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Osteosarcoma | Total | Non-Brainstem High-Grade Glioma | Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Ependymoma | Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Neuroblastoma (Measureable Disease) | Rhabdomyosarcoma | Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 14.94 years STANDARD_DEVIATION 4.28 | 11.96 years STANDARD_DEVIATION 5.97 | 12.75 years STANDARD_DEVIATION 5.15 | 12.00 years STANDARD_DEVIATION 7.13 | 8.42 years STANDARD_DEVIATION 4.59 | 9.62 years STANDARD_DEVIATION 5.38 | 6.23 years STANDARD_DEVIATION 2.98 | 8.74 years STANDARD_DEVIATION 4.96 | 18.24 years STANDARD_DEVIATION 3.35 |
| Karnofsky Performance Score 100 | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Karnofsky Performance Score 50 | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Karnofsky Performance Score 70 | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Karnofsky Performance Score 80 | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Karnofsky Performance Score 90 | 3 Participants | 9 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Karnofsky Performance Score Missing | 6 Participants | 54 Participants | 8 Participants | 8 Participants | 9 Participants | 5 Participants | 5 Participants | 9 Participants | 4 Participants |
| Lansky Play Score 100 | 1 Participants | 18 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants |
| Lansky Play Score 50 | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Lansky Play Score 60 | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Lansky Play Score 70 | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Lansky Play Score 80 | 2 Participants | 11 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Lansky Play Score 90 | 1 Participants | 18 Participants | 4 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants |
| Lansky Play Score Missing | 4 Participants | 18 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 14 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 48 Participants | 6 Participants | 8 Participants | 9 Participants | 4 Participants | 2 Participants | 7 Participants | 8 Participants |
| Region of Enrollment Canada | 3 participants | 11 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 1 participants | 4 participants |
| Region of Enrollment United States | 7 participants | 61 participants | 10 participants | 10 participants | 9 participants | 5 participants | 5 participants | 8 participants | 7 participants |
| Sex: Female, Male Female | 4 Participants | 32 Participants | 5 Participants | 4 Participants | 3 Participants | 1 Participants | 1 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 40 Participants | 5 Participants | 7 Participants | 7 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 72 |
| serious Total, serious adverse events | 21 / 72 |
Outcome results
Primary
Percentage of Participants With Overall Tumor Response (Response Rate)
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response = disappearance of all target lesions. Partial Response = 30% decrease in sum of longest diameter of target lesions. Response rate (percent \[%\])= (number of participants with complete response (CR) or partial response (PR) in stratum/number of participants in stratum)\*100.
Time frame: baseline to measured progressive disease (up to 1 year)
Population: All treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osteosarcoma | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Rhabdomyosarcoma | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Neuroblastoma (Measureable Disease) | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Ependymoma | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
| Non-Brainstem High-Grade Glioma | Percentage of Participants With Overall Tumor Response (Response Rate) | 0 Percentage of Participants |
Secondary
Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug
AdEERS= Adverse Event Expedited Reporting System; AE = adverse event. Patients may be counted in more than 1 category. Includes events that were considered possibly related to study drug (PRSD) as judged by the investigator.
Time frame: every cycle (up to 2 years and 7 months)
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Osteosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Osteosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Osteosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Osteosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 3 Participants |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 2 Participants |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 1 Participants |
| Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Rhabdomyosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Rhabdomyosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Rhabdomyosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 0 Participants |
| Rhabdomyosarcoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Neuroblastoma (Measureable Disease) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Neuroblastoma (Measureable Disease) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Neuroblastoma (Measureable Disease) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 2 Participants |
| Neuroblastoma (Measureable Disease) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 3 Participants |
| Ependymoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 2 Participants |
| Ependymoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Ependymoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Ependymoma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 2 Participants |
| Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 2 Participants |
| Non-Brainstem High-Grade Glioma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died on therapy possibly related to study drug | 0 Participants |
| Non-Brainstem High-Grade Glioma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Discontinued due to AE possibly related to drug | 0 Participants |
| Non-Brainstem High-Grade Glioma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | Died within 31 days of last dose of drug PRSD | 0 Participants |
| Non-Brainstem High-Grade Glioma | Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug | >=1 AdEERs possibly related to study drug | 2 Participants |
Secondary
Pharmacogenomics - Measure the Response of Genes Related to Toxicity
The pharmacogenomics outcomes examining the correlation between the presence of the methylene tetrahydrofolate reductase gene and the presence of a polymorphism in the thymidylate synthase (TS) gene and/or gene promoter and toxicity were optional and will not be reported here. Results of this optional research may be reported in the future by the Children's Oncology Group in the peer-reviewed literature.
Time frame: baseline
Population: The pharmacogenomics outcomes examining the correlation between the presence of the methylene tetrahydrofolate reductase gene and the presence of a polymorphism in the thymidylate synthase (TS) gene and/or gene promoter and toxicity were optional and will not be reported here.