Pemetrexed Disodium in Treating Patients With Recurrent Malignant Gliomas, Primary CNS Lymphoma, or Brain Metastases

Sponsor

Northwestern University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00276783

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

205

Duration (Months)

15.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with recurrent malignant gliomas, primary CNS lymphoma, or brain metastases.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma Metastatic Cancer	Drug: pemetrexed	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the 6-month progression-free survival rate in patients with recurrent malignant gliomas treated with pemetrexed disodium.
Determine the time to progression in patients with recurrent malignant gliomas, primary CNS lymphoma (PCNSL), or brain metastases treated with pemetrexed disodium.

Secondary

Determine the radiographic response in patients with recurrent malignant gliomas, PCNSL, or brain metastases treated with pemetrexed disodium.
Determine the time to response in patients treated with this drug.
Determine the duration of response in patients treated with this drug.
Determine the overall survival of patients treated with this drug.
Collect safety data on patients with intracranial tumors treated with this drug.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Alimta (Pemetrexed) in Patients With Recurrent Malignant Gliomas, Primary Central Nervous System Lymphoma, and Brain Metastases

Study Start Date :

Nov 1, 2005

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Pemetrexed 900 mg/m2 every 21 days until disease progression.	Drug: pemetrexed Administered intravenously at a dose of 900 mg/m2 every 21 days until disease progression. Other Names: pemetrexed disodium Alimta

Arm

Intervention/Treatment

Experimental: Treatment Arm

Pemetrexed 900 mg/m2 every 21 days until disease progression.

Drug: pemetrexed

Administered intravenously at a dose of 900 mg/m2 every 21 days until disease progression.

Other Names:

pemetrexed disodium

Alimta

Outcome Measures

Primary Outcome Measures

Progression free survival at 6 months and time to disease progression [After every 2 cycles of therapy (1 cycle = 3 weeks) until disease progression]

Secondary Outcome Measures

Radiographic response [After 6 months of treatment]
Collect safety data [After every cycle of therapy (cycle = 3 weeks) until disease progression or death.]
Overall survival [After every cycle of treatment (1 cycle = 3 weeks) until death]
Compare blood and tissue methylation patterns and correlate with response. [Blood and tissue from baseline, then additional blood every 6 weeks while on treatment]
This was optional for patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
Malignant glioma, including the following subtypes: glioblastoma or gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, or malignant glioma not otherwise specified, meeting the following criteria:
Not required to have measurable or evaluable disease
Must have failed prior radiation therapy > 4 weeks ago
Must have failed at least 1 prior chemotherapy regimen
Confirmation of tumor progression by MR spectroscopy, PET scan, or biopsy/resection if prior radiosurgery was performed
Primary CNS lymphoma, meeting the following criteria:
Measurable disease as defined by bidimensionally measurable lesions with clearly defined margins by CT scan or MRI
Must have failed at least one prior chemotherapy regimen
Must have failed at least one agent or regimen
Brain metastases from a solid tumor, meeting the following criteria:
Measurable disease as defined by bidimensionally measurable lesions with clearly defined margins by CT scan or MRI
Biopsy is not required if radiographic imaging is consistent with brain metastases
Must have failed prior whole-brain radiotherapy
Patients with leptomeningeal metastases with or without brain metastases are eligible for therapy (may be diagnosed by MRI or cytology)
Confirmation of tumor progression by MR spectroscopy, PET scan, or biopsy/resection if prior radiosurgery was performed
Effusions or fluid collections must be drained prior to study entry

PATIENT CHARACTERISTICS:

Karnofsky performance score ≥ 60
WBC > 3,000/mm^3
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
Hemoglobin > 10 mg/dL (transfusion allowed)
SGOT/SGPT < 3.0 times upper limit of normal (ULN)
Bilirubin < 1.5 times ULN
Creatinine < 1.5 mg/dL
Creatinine clearance > 45 mL/min
Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study and for 3 months after completing study treatment
Women who are pregnant or breast-feeding are not eligible for study treatment
Negative pregnancy test
Able to take steroids, vitamin B12, or folate
No significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
Only one active tumor type allowed, except nonmelanoma skin cancer or carcinoma in situ of the cervix
A history of other malignancies are acceptable if in complete remission and off all therapy for that disease for a minimum of 3 years

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 4 weeks since prior whole-brain or other radiotherapy
Recovered from any side effects (6 weeks for a nitrosourea; 4 weeks for temozolomide, procarbazine, etoposide or experimental agent; 3 weeks for isotretinoin or tamoxifen) (for patients with gliomas)
No more than 2 prior chemotherapeutic agents or regimens (includes biologic agents) (for patients with gliomas)
Recovered from prior biopsy or re-resection of the tumor (10-14 days for resection or 3-5 days for a biopsy) (for patients with gliomas)
May not be on any other chemotherapy except for hormonal therapy or trastuzumab (Herceptin®) (for patients with brain metastases)
No limitations on prior CNS-directed therapies (for patients with brain metastases)
Able to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs)
Patients taking NSAIDs or aspirin are required to interrupt therapy for at least 2 days before the study treatment and 2 days after the infusion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology-Oncology Associates of Illinois	Chicago	Illinois	United States	60611-2998
2	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013