Chemotherapy for Patients With Osteosarcoma

Study Overview
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Brief Summary
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The primary purpose of your participation in this study is to help answer the following research questions, and not to provide you treatment for your condition. To assess how well treatment with pemetrexed works for patients with your type of cancer To assess for any side effects that might be associated with pemetrexed. To look at the characteristics and levels of certain of your genes and proteins to learn more about osteosarcoma and how pemetrexed works in your body.

Official Title
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Phase II Trial of Pemetrexed in Second Line Advanced/Metastatic Osteosarcomas

Conditions
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Osteosarcoma

Intervention / Treatment
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* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of high grade locally advanced or metastatic osteosarcoma Must have one prior chemotherapy regimen for advanced disease At least 1 unidimensional measurable lesion by computed tomography (CT) scan Have a good performance status Adequate organ function Exclusion Criteria: Have a serious concomitant systemic disorder (for example active Human Immunodeficiency Virus infection) Have brain metastases not adequately treated Significant weight loss (that is more than 20%) over the previous 6 weeks before study entry Inability or unwillingness to take folic acid or vitamin B12 supplementation and corticosteroids Pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed<br>Participants received pemetrexed 500 milligrams per square meter (mg/m^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle. | Drug: Pemetrexed<br>* 500 mg/m^2, IV every 21 days until disease progression, unacceptable toxicity, participant or physician's decision.<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Tumor Response | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) = at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD) = small changes that do not meet above criteria. Tumor Response Rate(%) = sum of number of PR + CR observed/number of participants qualified for tumor response analysis * 100. | Baseline to 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Treatment Failure | When the protocol was written, time to treatment failure (TTTF) was included as a secondary endpoint. However, it was subsequently realized that due to the design of the study, participants are treated until disease progression or discontinuation from study treatment, not for a fixed number of cycles. Therefore, it was concluded that analysis of TTTF was inappropriate with the current study design and the analysis was not conducted, since it would be essentially the same as Progression-Free Survival. | Baseline to 21 months | 
| Correlation of Disease Outcome With Pharmacogenomic Analysis | It was planned to examine methylthioadenosine phosphorylase (MTAP) gene deletion, folate receptor alpha (FRα) and folylpoly-gamma-glutamate synthetase (FPGS) expression, and to correlate the results with the clinical data to determine the association between these factors and clinical outcome to treatment. However, due to the small number of participants with partial response (n=1), the planned statistical analyses that would correlate responders/non responders with pharmacogenomics data are no longer valid and the analyses were not conducted. | Baseline to 21 months | 
| Number of Participants With Adverse Events (Pharmacology Toxicity) | Pharmacology toxicity was defined as serious and non-serious adverse events. Summaries of these adverse events are located in the Reported Adverse Event Section. | Baseline to 21 months | 
| Duration of Response | The duration of a complete response (CR) or partial response (PR) was defined as the time from the first objective status assessment of CR or PR to the first date of progression or death as a result of any cause: CR was achieved if all tumor lesions disappeared; PR was achieved if there was >=30% decrease in sum of the longest diameter (LD) of target lesions (reference: baseline sum LDs) or complete disappearance of target lesions with persistence (but not worsening) of >=1 nontarget lesions and no appearance of new lesions. | Baseline to 31 months | 
| Progression-Free Survival (PFS) | PFS was from date of study enrollment to first date of objectively determined progressive disease (PD) or death from any cause. For participants who did not die as of data cut-off date and who did not have objective PD, PFS was censored at date of last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from study drug) before objectively determined disease progression or death, PFS was censored at date of last objective progression-free disease assessment, before post-discontinuation chemotherapy. | Baseline to 10.4 months | 
| Overall Survival (OS) Time | OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact. | Baseline to 27.6 months |