Phase II Trial of Pemetrexed in Second Line Advanced/Metastatic Osteosarcomas - ND

• Conditions: Advanced/metastatic osteosarcomas; MedDRA version: 9.1Level: LLTClassification code 10031294Term: Osteosarcoma metastatic

• Registration Number: EUCTR2007-000912-97-IT
• Lead Sponsor: ELI LILLY

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-10
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

[1] Histological diagnosis of high grade locally advanced or metastatic osteosarcoma (World Health Organization (WHO) classification), not amenable to surgery, radiation, or combined modality therapy with curative intent. [2] One prior chemotherapy regimen for advanced disease; neo-adjuvant is not counted towards this requirement. Pemetrexed is considered as second line chemotherapy for advanced/metastatic disease. [3] At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST; Therasse et al. 2000; Protocol Attachment S115.5) criteria (at least 10 mm in longest diameter by spiral computerized tomography (CT) scan, or at least 20 mm by standard techniques). Positron emission tomography (PET) scans and ultrasounds may not be used. At least one measurable lesion outside of the field of any prior radiation therapy (according to RECIST criteria). Prior radiotherapy to a single index lesion is not allowed. Osseous lesions with soft tissue tumor at study entry (excluding completely calcified or necrosed lesion) are considered measurable lesions. [4] Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale (Protocol Attachment S115.3). [5] Adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.0 x 109/L, platelets ≥100 x 109/L (in case of bone marrow disease: ≥75 x 109/L), and hemoglobin ≥9.0g/dL. Hepatic: bilirubin ≤1.5 times the upper limit of normal ( ULN), alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) ≤3.0  ULN (AP, AST, and ALT ≤5  ULN is acceptable if the liver has tumor involvement). Renal: calculated creatinine clearance (CrCl) ≥45 mL/min based on the standard Cockcroft and Gault formula (Protocol Attachment S115.4). [6] Estimated life expectancy of at least 12 weeks. [7] Patient compliance and geographic proximity that allow adequate follow-up. [8] Prior radiation therapy allowed to <25% of the bone marrow. Prior radiotherapy must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. [9] Patients must sign an informed consent document. [10] Patients must be at least 18 years of age. [11] Fully recovered from any previous surgery and prior chemotherapy (at least 4 weeks since major surgery or prior myelosuppressive chemotherapy). With the exception of alopecia, patients must have resolution of all acute toxic effects of any prior surgery or chemotherapy to NCI-CTC (Version 3.0) grade ≤ 1. [12] For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 6 months after the treatment period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of sub

Exclusion Criteria

[13] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [14] Have previously completed or withdrawn from this study or any other study investigating pemetrexed. [15] Inability to comply with protocol or study procedures. [16] Have a serious concomitant systemic disorder (e.g. active infection including Human Immunodeficiency Virus (HIV)) that, in the opinion of the investigator, would compromise the patient?s safety or the patient?s ability to adhere to the protocol. [17] Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV (Protocol Attachment S115.6). [18] Have a concurrent serious infection. [19] Have a psychiatric disorder that prevents patients from providing informed consent or following protocol instructions. No other severe medical illness, including psychosis and previous history of severe cardiovascular disease. [20] Have a prior malignancy other than osteosarcoma, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously. [21] Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening CT or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. [22] Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that can not be controlled by drainage or other procedures prior to study entry. [23] Significant weight loss (that is 20%) over the previous 6 weeks before study entry. [24] Concurrent administration of any other antitumor therapy. [25] Inability to discontinue administration of aspirin at a dose >1.3 g/day or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam). [26] Inability or unwillingness to take folic acid or vitamin B12 supplementation. [27] Inability to take corticosteroids. [28] Pregnant or breast-feeding. [29] Have had a recent (within 30 days of study treatment) or concurrent yellow fever vaccination.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified