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

NCT01313884 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB-20323SU-03082011-7559SARCOMA0007
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Bone Cancer; Ewing's Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Progression-free Survival (PFS)

  24 months

Study Arms (1)

Combination Therapy

EXPERIMENTAL

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; Drug: Vincristine; Drug: Temozolomide; Drug: Doxorubicin; Drug: Cytoxan; Drug: Pegfilgrastim

Interventions

Irinotecan DRUG

50 mg/m2/day x 5 days

Also known as: Camptosar, Campto

Combination Therapy

Vincristine DRUG

2 mg/m2 to a maximum of 2 mg

Also known as: Oncovin, leurocristine

Combination Therapy

Temozolomide DRUG

100 mg/m2/day x 5 days followed by 2 weeks treatment-free

Also known as: Temodar, Temodal

Combination Therapy

Doxorubicin DRUG

Starting dose 75 mg/m2 to a maximum of 450mg/m2

Also known as: Adriamycin, hydroxydaunorubicin

Combination Therapy

Cytoxan DRUG

1200 mg/m2

Also known as: Cyclophosphamide, Endoxan, Neosar, Procytox, Revimmune, cytophosphane

Combination Therapy

Pegfilgrastim DRUG

6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle

Also known as: Neulasta

Combination Therapy

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead
• Amgen: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Bone Neoplasms; Sarcoma, Ewing

Interventions

Irinotecan; Vincristine; Temozolomide; Doxorubicin; Cyclophosphamide; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Study did not reach primary objective; study didn't accrue enough patients.

Results Point of Contact

• Title: Kristen Ganjoo, MD
• Organization: Stanford University Medical Center

kganjoo@stanford.edu

650-725-6413

Study Officials

• Kristen N. Ganjoo

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 14, 2011
• Study Start: May 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 24, 2017
• Results First Posted: February 2, 2017

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)