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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00276783
• Other study ID #: NU 05C2
• Secondary ID: P30CA060553NU-05
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 2005
• Est. completion date: December 2022

Study information

• Verified date: March 2020
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Lymphoma
• Metastatic Cancer
• Nervous System Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Hematology-Oncology Associates of Illinois	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

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