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A Study of Pemetrexed in Children With Recurrent Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00520936
Collaborator
Children's Oncology Group (Other)
72
Enrollment
1
Location
1
Arm
29
Duration (Months)
2.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Pemetrexed in Children With Recurrent Malignancies
Study Start Date :
Sep 1, 2007
Actual Primary Completion Date :
Feb 1, 2010
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pemetrexed

Drug: pemetrexed
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
Other Names:
  • LY 231514
  • Alimta

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 22 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Arcadia California United States 91066

    Sponsors and Collaborators

    • Eli Lilly and Company
    • Children's Oncology Group

    Investigators

    • Study Director: 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00520936
    Other Study ID Numbers:
    • 10294
    • H3E-MC-JMHW
    • ADVL0525
    • NCT00459147
    • NCT00739427
    First Posted:
    Aug 27, 2007
    Last Update Posted:
    Feb 25, 2011
    Last Verified:
    Feb 1, 2011
    Additional relevant MeSH terms:
    Neuroblastoma
    Osteosarcoma
    Rhabdomyosarcoma
    Ependymoma
    Medulloblastoma
    Sarcoma, Ewing
    Neuroectodermal Tumors, Primitive, Peripheral
    Pemetrexed

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Osteosarcoma Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Rhabdomyosarcoma Neuroblastoma (Measureable Disease) Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Ependymoma Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Non-Brainstem High-Grade Glioma
    Arm/Group Description Pemetrexed 1910 milligrams per meters squared (mg/m^2) (or 60 milligrams per kilogram [mg/kg] if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old)
    Period Title: Overall Study
    STARTED 10 11 9 5 6 10 11 10
    COMPLETED 10 7 7 5 5 10 7 9
    NOT COMPLETED 0 4 2 0 1 0 4 1

    Baseline Characteristics

    Arm/Group Title Osteosarcoma Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Rhabdomyosarcoma Neuroblastoma (Measureable Disease) Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Ependymoma Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Non-Brainstem High-Grade Glioma Total
    Arm/Group Description Pemetrexed 1910 milligrams per meters squared (mg/m^2) (or 60 milligrams per kilogram [mg/kg] if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Total of all reporting groups
    Overall Participants 10 11 9 5 6 10 11 10 72
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    14.94
    (4.28)
    18.24
    (3.35)
    8.74
    (4.96)
    6.23
    (2.98)
    9.62
    (5.38)
    8.42
    (4.59)
    12.00
    (7.13)
    12.75
    (5.15)
    11.96
    (5.97)
    Sex: Female, Male (Count of Participants)
    Female
    4
    40%
    8
    72.7%
    6
    66.7%
    1
    20%
    1
    16.7%
    3
    30%
    4
    36.4%
    5
    50%
    32
    44.4%
    Male
    6
    60%
    3
    27.3%
    3
    33.3%
    4
    80%
    5
    83.3%
    7
    70%
    7
    63.6%
    5
    50%
    40
    55.6%
    Race/Ethnicity, Customized (Number) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    2.8%
    Asian
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    2
    2.8%
    Black or African American
    4
    40%
    0
    0%
    0
    0%
    2
    40%
    1
    16.7%
    1
    10%
    3
    27.3%
    3
    30%
    14
    19.4%
    White
    4
    40%
    8
    72.7%
    7
    77.8%
    2
    40%
    4
    66.7%
    9
    90%
    8
    72.7%
    6
    60%
    48
    66.7%
    Other
    1
    10%
    1
    9.1%
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    4.2%
    Unknown
    1
    10%
    1
    9.1%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    3
    4.2%
    Region of Enrollment (participants) [Number]
    United States
    7
    70%
    7
    63.6%
    8
    88.9%
    5
    100%
    5
    83.3%
    9
    90%
    10
    90.9%
    10
    100%
    61
    84.7%
    Canada
    3
    30%
    4
    36.4%
    1
    11.1%
    0
    0%
    1
    16.7%
    1
    10%
    1
    9.1%
    0
    0%
    11
    15.3%
    Karnofsky Performance Score (Number) [Number]
    100
    0
    0%
    2
    18.2%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    3
    4.2%
    90
    3
    30%
    3
    27.3%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    9.1%
    1
    10%
    9
    12.5%
    80
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    2
    2.8%
    70
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    2
    2.8%
    50
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    2
    2.8%
    Missing
    6
    60%
    4
    36.4%
    9
    100%
    5
    100%
    5
    83.3%
    9
    90%
    8
    72.7%
    8
    80%
    54
    75%
    Lansky Play Score (Number) [Number]
    100
    1
    10%
    1
    9.1%
    3
    33.3%
    4
    80%
    2
    33.3%
    2
    20%
    2
    18.2%
    3
    30%
    18
    25%
    90
    1
    10%
    3
    27.3%
    3
    33.3%
    1
    20%
    1
    16.7%
    2
    20%
    3
    27.3%
    4
    40%
    18
    25%
    80
    2
    20%
    0
    0%
    2
    22.2%
    0
    0%
    2
    33.3%
    3
    30%
    2
    18.2%
    0
    0%
    11
    15.3%
    70
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    1
    10%
    2
    2.8%
    60
    1
    10%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    1
    10%
    1
    9.1%
    0
    0%
    4
    5.6%
    50
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    Missing
    4
    40%
    7
    63.6%
    0
    0%
    0
    0%
    1
    16.7%
    1
    10%
    3
    27.3%
    2
    20%
    18
    25%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Overall Tumor Response (Response Rate)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group Title Osteosarcoma Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Rhabdomyosarcoma Neuroblastoma (Measureable Disease) Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Ependymoma Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Non-Brainstem High-Grade Glioma
    Arm/Group Description Pemetrexed 1910 milligrams per meters squared (mg/m^2) (or 60 milligrams per kilogram [mg/kg] if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old)
    Measure Participants 10 11 9 5 6 10 11 10
    Number [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    All treated participants.
    Arm/Group Title Osteosarcoma Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Rhabdomyosarcoma Neuroblastoma (Measureable Disease) Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Ependymoma Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Non-Brainstem High-Grade Glioma
    Arm/Group Description Pemetrexed 1910 milligrams per meters squared (mg/m^2) (or 60 milligrams per kilogram [mg/kg] if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old)
    Measure Participants 10 11 9 5 6 10 11 10
    >=1 AdEERs possibly related to study drug
    3
    30%
    2
    18.2%
    0
    0%
    2
    40%
    3
    50%
    2
    20%
    2
    18.2%
    2
    20%
    Discontinued due to AE possibly related to drug
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    18.2%
    0
    0%
    Died on therapy possibly related to study drug
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Died within 31 days of last dose of drug PRSD
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Pharmacogenomics - Measure the Response of Genes Related to Toxicity
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Osteosarcoma Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors Rhabdomyosarcoma Neuroblastoma (Measureable Disease) Neuroblastoma (Metaiodobenzylguanidine Positive Evaluable) Ependymoma Medulloblastoma/Supratentorial Primitive Neuroectodermal Tumor Non-Brainstem High-Grade Glioma
    Arm/Group Description Pemetrexed 1910 milligrams per meters squared (mg/m^2) (or 60 milligrams per kilogram [mg/kg] if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old) Pemetrexed 1910 mg/m^2 (or 60 mg/kg if patient <12 months old)
    Measure Participants 0 0 0 0 0 0 0 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Pemetrexed
    Arm/Group Description Pemetrexed 1910 mg/m2 (or 60 mg/kg if patient <12 months old)
    All Cause Mortality
    Pemetrexed
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Pemetrexed
    Affected / at Risk (%) # Events
    Total 21/72 (29.2%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/72 (5.6%) 4
    Hemoglobin 1/72 (1.4%) 1
    Infection 2/72 (2.8%) 2
    Infection with normal ANC or Grade 1 4/72 (5.6%) 4
    Leukocytes 3/72 (4.2%) 3
    Lymphopenia 3/72 (4.2%) 3
    Neutrophils/granulocytes 3/72 (4.2%) 3
    Platelets 2/72 (2.8%) 2
    Gastrointestinal disorders
    Nausea 2/72 (2.8%) 2
    Pain: Tumor pain 1/72 (1.4%) 1
    Ulceration 1/72 (1.4%) 1
    Vomiting 2/72 (2.8%) 2
    General disorders
    Fever 1/72 (1.4%) 1
    Flushing 1/72 (1.4%) 1
    Pain: Extremity-limb 1/72 (1.4%) 1
    Infections and infestations
    Dyspnea 2/72 (2.8%) 2
    Rash/desquamation 1/72 (1.4%) 1
    Investigations
    GGT 1/72 (1.4%) 1
    Metabolism and nutrition disorders
    Albumin, serum-low 1/72 (1.4%) 1
    Calcium, serum-low 1/72 (1.4%) 1
    Dehydration 1/72 (1.4%) 1
    Phosphate, serum-low 3/72 (4.2%) 3
    Potassium, serum-low 2/72 (2.8%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hemorrhage, CNS 1/72 (1.4%) 1
    Nervous system disorders
    Hydrocephalus 1/72 (1.4%) 1
    Hypotension 1/72 (1.4%) 1
    Mood alteration: Depression 1/72 (1.4%) 1
    Syncope 1/72 (1.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Death not associated with CTCAE term 3/72 (4.2%) 3
    Skin and subcutaneous tissue disorders
    Rash: erythema multiforme 1/72 (1.4%) 1
    Other (Not Including Serious) Adverse Events
    Pemetrexed
    Affected / at Risk (%) # Events
    Total 10/72 (13.9%)
    Blood and lymphatic system disorders
    Infection with normal ANC or Grade 1 2/72 (2.8%) 2
    Cardiac disorders
    Dermatology/Skin - Other 1/72 (1.4%) 1
    Pulmonary/Upper Respiratory - Other 1/72 (1.4%) 1
    Thrombosis/thrombus/embolism 1/72 (1.4%) 1
    Congenital, familial and genetic disorders
    Sodium, serum-low 1/72 (1.4%) 1
    Gastrointestinal disorders
    Diarrhea 1/72 (1.4%) 1
    Hemorrhage, GI: Rectum 1/72 (1.4%) 1
    Pain: Tumor pain 1/72 (1.4%) 1
    General disorders
    Fever 2/72 (2.8%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Seizure 2/72 (2.8%) 2
    Renal and urinary disorders
    Hemorrhage, GU: Urinary NOS 1/72 (1.4%) 1
    Renal failure 1/72 (1.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 2/72 (2.8%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00520936
    Other Study ID Numbers:
    • 10294
    • H3E-MC-JMHW
    • ADVL0525
    • NCT00459147
    • NCT00739427
    First Posted:
    Aug 27, 2007
    Last Update Posted:
    Feb 25, 2011
    Last Verified:
    Feb 1, 2011