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

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

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.

Study Overview

• Status: Terminated
• Conditions: Bone Cancer; Ewing's Sarcoma
• Intervention / Treatment: Drug: Irinotecan; Drug: Vincristine; Drug: Temozolomide; Drug: Doxorubicin; Drug: Cytoxan; Drug: Pegfilgrastim

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Therapy; 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; 50 mg/m2/day x 5 days; Other Names: Campto; Camptosar; Drug: Vincristine; 2 mg/m2 to a maximum of 2 mg; Other Names: Oncovin; leurocristine; Drug: Temozolomide; 100 mg/m2/day x 5 days followed by 2 weeks treatment-free; Other Names: Temodar; Temodal; Drug: Doxorubicin; Starting dose 75 mg/m2 to a maximum of 450mg/m2; Other Names: Adriamycin; hydroxydaunorubicin; Drug: Cytoxan; 1200 mg/m2; Other Names: Endoxan; Neosar; Revimmune; Cyclophosphamide; Procytox; cytophosphane; Drug: Pegfilgrastim; 6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle; 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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Amgen
• Investigators: Principal Investigator: Kristen N. Ganjoo, Stanford University

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Actual): November 24, 2017
• Last Update Submitted That Met QC Criteria: October 20, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Bone Diseases; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Bone Neoplasms; Sarcoma, Ewing; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Cyclophosphamide; Temozolomide; Irinotecan; Doxorubicin; Vincristine
• Other Study ID Numbers: IRB-20323; SU-03082011-7559 (Other Identifier: Stanford University); SARCOMA0007 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO