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

Phase 2

Terminated

Conditions: Bone Cancer
Ewing's Sarcoma

Interventions: Drug: Irinotecan
Drug: Vincristine
Drug: Temozolomide
Drug: Doxorubicin
Drug: Cytoxan
Drug: Pegfilgrastim

Registration Number: NCT01313884

Lead Sponsor: Stanford University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination Therapy	Pegfilgrastim	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
Combination Therapy	Cytoxan	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
Combination Therapy	Irinotecan	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
Combination Therapy	Vincristine	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
Combination Therapy	Temozolomide	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
Combination Therapy	Doxorubicin	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.