Osteosarcoma
Conditions
Brief summary
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.
Interventions
DRUGPemetrexed
500 mg/m\^2, IV every 21 days until disease progression, unacceptable toxicity, participant or physician's decision.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tumor Response | Baseline to 21 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Disease Outcome With Pharmacogenomic Analysis | Baseline to 21 months | 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. |
| Number of Participants With Adverse Events (Pharmacology Toxicity) | Baseline to 21 months | Pharmacology toxicity was defined as serious and non-serious adverse events. Summaries of these adverse events are located in the Reported Adverse Event Section. |
| Time to Treatment Failure | Baseline to 21 months | 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. |
| Progression-Free Survival (PFS) | Baseline to 10.4 months | 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. |
| Overall Survival (OS) Time | Baseline to 27.6 months | OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact. |
| Duration of Response | Baseline to 31 months | 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. |
Countries
France, Germany, Italy, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed 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 | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death due to Adverse Event | 2 |
| Overall Study | Death due to Study Disease | 4 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive Disease | 22 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| Age Continuous | 42.1 years STANDARD_DEVIATION 16.28 |
| Best Response of Last Prior Treatment Regimen for Osteosarcoma Complete Response | 1 participants |
| Best Response of Last Prior Treatment Regimen for Osteosarcoma Not Applicable | 3 participants |
| Best Response of Last Prior Treatment Regimen for Osteosarcoma Partial Response | 3 participants |
| Best Response of Last Prior Treatment Regimen for Osteosarcoma Progressive Disease | 15 participants |
| Best Response of Last Prior Treatment Regimen for Osteosarcoma Stable Disease | 10 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG Performance Status 0 | 16 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG Performance Status 1 | 14 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG Performance Status 2 | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG Performance Status Not Available | 1 participants |
| Histopathological Diagnosis of Osteosarcoma at Study Entry | 32 participants |
| Number of non target lesions 0 Non Target Lesions | 10 participants |
| Number of non target lesions 1 Non Target Lesion | 15 participants |
| Number of non target lesions 2 Non Target Lesions | 5 participants |
| Number of non target lesions 3 Non Target Lesions | 1 participants |
| Number of non target lesions 5 Non Target Lesions | 1 participants |
| Number of Target Lesions 0 Target Lesions | 1 participants |
| Number of Target Lesions 1 Target Lesion | 9 participants |
| Number of Target Lesions 2 Target Lesions | 8 participants |
| Number of Target Lesions 3 Target Lesions | 4 participants |
| Number of Target Lesions 4 Target Lesions | 3 participants |
| Number of Target Lesions 5 Target Lesions | 7 participants |
| Pathological Diagnosis of Osteosarcoma at Study Entry | 32 participants |
| Region of Enrollment France | 13 participants |
| Region of Enrollment Germany | 6 participants |
| Region of Enrollment Italy | 9 participants |
| Region of Enrollment Spain | 3 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 20 Participants |
| Time from last diagnosis to enrollment | 13.3 days STANDARD_DEVIATION 12.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 32 |
| serious Total, serious adverse events | 11 / 32 |
Outcome results
Primary
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.
Time frame: Baseline to 21 months
Population: Participants who qualified for tumor response analysis are those with histological evidence of high grade locally advanced or metastatic osteosarcoma and treatment with at least 1 dose of study drug. Three participants died before the first tumor assessment and 1 participant discontinued without any tumor assessments and were considered Unknown.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed | Percentage of Participants With Tumor Response | Response Rate | 3.1 percentage of participants |
| Pemetrexed | Percentage of Participants With Tumor Response | Complete Response (CR) | 0 percentage of participants |
| Pemetrexed | Percentage of Participants With Tumor Response | Partial Response (PR) | 3.1 percentage of participants |
| Pemetrexed | Percentage of Participants With Tumor Response | Stable Disease (SD) | 15.6 percentage of participants |
| Pemetrexed | Percentage of Participants With Tumor Response | Progressive Disease (PD) | 68.8 percentage of participants |
| Pemetrexed | Percentage of Participants With Tumor Response | Unknown | 12.5 percentage of participants |
Secondary
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.
Time frame: Baseline to 21 months
Population: Since this outcome measure was not analyzed due to the inadequate number of responders, zero participants were analyzed.
Secondary
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.
Time frame: Baseline to 31 months
Population: Tumor response population: participants with best overall response of complete response (CR) and partial response (PR).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed | Duration of Response | 9.5 months |
Secondary
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.
Time frame: Baseline to 21 months
Population: Full analysis population: all participants who were treated with at least one dose of the study regimen
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed | Number of Participants With Adverse Events (Pharmacology Toxicity) | Serious Adverse Events | 11 participants |
| Pemetrexed | Number of Participants With Adverse Events (Pharmacology Toxicity) | All Other Nonserious Adverse Events | 26 participants |
Secondary
Overall Survival (OS) Time
OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact.
Time frame: Baseline to 27.6 months
Population: Full analysis population: all participants who were treated with at least one dose of the study regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Overall Survival (OS) Time | 5.5 months |
Secondary
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.
Time frame: Baseline to 10.4 months
Population: Full analysis population: all participants who were treated with at least one dose of the study regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed | Progression-Free Survival (PFS) | 1.4 months |
Secondary
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.
Time frame: Baseline to 21 months
Population: Since this outcome measure was not analyzed due to the study design, zero participants were analyzed.