Cyclophosphamide, Doxorubicin, Vincristine w/ Irinotecan and Temozolomide in Ewings Sarcoma

Study Overview
=================
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.

Official Title
-----------------
A Phase II Pilot Study of Cyclophosphamide, Doxorubicin, Vincristine Alternating With Irinotecan and Temozolomide in Patients With Newly Diagnosed Metastatic Ewing's Sarcoma

Conditions
-----------------
Bone Cancer, Ewing's Sarcoma

Intervention / Treatment
-----------------
* Drug: Irinotecan
* Drug: Vincristine
* Drug: Temozolomide
* Drug: Doxorubicin
* Drug: Cytoxan
* Drug: Pegfilgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 13 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br>Regimen A alternating with Regimen B every 21 days Regimen A: Cytoxan 1200mg/m2 Doxorubicin, starting dose 75 mg/m2 to a maximum of 450mg/m2 Vincristine, starting dose 2 mg/m2 to a maximum of 2 mg Pegfilgrastim, 6 mg subcutaneous within 24 to 48 hours after each cycle Regimen B: Irinotecan 50 mg/m2/day x 5 days Temozolomide 100 mg/m2/day x 5 days followed by 2 weeks treatment-free | Drug: Irinotecan<br>* 50 mg/m2/day x 5 days<br>* Other names: Campto;Drug: Vincristine<br>* 2 mg/m2 to a maximum of 2 mg<br>* Other names: leurocristine;Drug: Temozolomide<br>* 100 mg/m2/day x 5 days followed by 2 weeks treatment-free<br>* Other names: Temodal;Drug: Doxorubicin<br>* Starting dose 75 mg/m2 to a maximum of 450mg/m2<br>* Other names: hydroxydaunorubicin;Drug: Cytoxan<br>* 1200 mg/m2<br>* Other names: cytophosphane;Drug: Pegfilgrastim<br>* 6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle<br>* Other names: Neulasta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | The intended outcome is a measure of whether participants are alive without disease progression 2 years (24 months) after treatment. | 24 months |