Bone Cancer, Ewing's Sarcoma
Conditions
Brief summary
The outcome of patients with metastatic Ewings Sarcoma is poor with current standard of care chemotherapy, with less than 30% survival. Based on recent encouraging pediatric literature we have designed this trial to improve the outcome of patients with metastatic Ewings sarcoma using Irinotecan and Temozolomide in addition to standard chemotherapy.
Interventions
DRUGIrinotecan
50 mg/m2/day x 5 days
DRUGVincristine
2 mg/m2 to a maximum of 2 mg
DRUGTemozolomide
100 mg/m2/day x 5 days followed by 2 weeks treatment-free
DRUGDoxorubicin
Starting dose 75 mg/m2 to a maximum of 450mg/m2
DRUGCytoxan
1200 mg/m2
DRUGPegfilgrastim
6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle
Sponsors
Amgen
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of metastatic Ewing's sarcoma. * Patients must have measurable disease defined as lesions that can be measured by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease, lesions seen on scan will not be considered measurable. * Patients must have metastatic disease. * Age 13 years or older * Life expectancy of at least 3 months. * ECOG performance status of \<= 3. * Normal hepatic function (Direct bilirubin \<1.5mg/dl, SGOT or SGPT \<3x upper limit of normal). * Left Ventricular Ejection fraction of at least 50%. * Adequate renal function: Creatinine clearance \>= 50 ml/min or Serum creatinine \< 1.5 x ULN for age. * Adequate bone marrow reserve (defined as an absolute peripheral granulocyte count of \>=1500/mm3, platelet count of \>=75,000/mm3); unless bone marrow infiltrated with metastatic Ewing's sarcoma; ANC \>= 500 and Platelet \>= 50,000 mm3. * Ability to understand and willing to sign a written informed consent document. * Patients of childbearing potential must agree to use an effective method of contraception.
Exclusion criteria
* No prior chemotherapy for Ewing's sarcoma; No prior doxorubicin, temozolomide or irinotecan. * Known hypersensitivity to any of the components of the protocol drugs. * Clinically significant unrelated systemic illness (such as serious infections requiring active systemic intravenous antibiotic therapy; cardiovascular disease \[congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension\]. * No prior history of chronic diarrhea, bowel obstruction, Crohn's disease or ulcerative colitis. * Pregnant or nursing woman are not included in the study. * HIV-positive patients will be excluded from the study due to risk of infection or other serious side effects. * Other medical, psychiatric or social condition incompatible with study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Partial and Complete Response) | Up to 24 months | Response was evaluated every 12 weeks during treatment. Subjects who discontinue treatment for reasons other than disease progression or initiation of new anticancer therapy (excluding radiation therapy and surgery) response evaluated every 6 months following the last dose of study drug. Scans should be obtained every 6 months for up to 2 years (24 months) or until progression of disease or initiation of new anticancer therapy. Complete response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 24 months | The intended outcome is a measure of whether participants are alive without disease progression 2 years (24 months) after treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination Therapy Regimen A alternate with Regimen B every 21 days
Regimen A:
Cytoxan=1200mg/m2 Doxorubicin=75mg/m2 (Maxiumum allowed dose 450mg/m2) Vincristine=2mg/m2 (capped at 2mg total dose)
Regimen B:
Irinotecan=50 mg/m2/day x 5 days Temozolomide=100 mg/m2/day x 5 days followed by two weeks of treatment-free period.
Irinotecan: 50 mg/m2/day x 5 days
Vincristine: 2 mg/m2 (capped at 2mg total do)
Temozolomide: 100 mg/m2/day x 5 days
Doxorubicin: 75 mg/m2
Cytoxan: 1200 mg/m2
Pegfilgrastim: 6 mg
Mesna: 240 mg/m2 in 50 ml NS | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Per insurance pvdr, pt can't be on cl tr | 1 |
Baseline characteristics
| Characteristic | Combination Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Overall Response Rate (Partial and Complete Response)
Response was evaluated every 12 weeks during treatment. Subjects who discontinue treatment for reasons other than disease progression or initiation of new anticancer therapy (excluding radiation therapy and surgery) response evaluated every 6 months following the last dose of study drug. Scans should be obtained every 6 months for up to 2 years (24 months) or until progression of disease or initiation of new anticancer therapy. Complete response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters.
Time frame: Up to 24 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy | Overall Response Rate (Partial and Complete Response) | Partial Response | 2 Participants |
| Combination Therapy | Overall Response Rate (Partial and Complete Response) | Complete Response | 0 Participants |
Secondary
Progression-free Survival (PFS)
The intended outcome is a measure of whether participants are alive without disease progression 2 years (24 months) after treatment.
Time frame: 24 months
Population: All study participants were lost to follow-up after completion of active treatment and collection of response rate, ie, within 2 years of the treatment conclusion but before documented progression. No data.