Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma

NCT00516295 | Completed Phase 2 Results DMC

• 3 other identifiers: NCI-2009-00369AEWS0521U10CA098543
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial study has a 6-patient feasibility portion studying the tolerability of chemotherapy with vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. If the therapy is considered tolerable, this feasibility run-in will be followed by a randomized phase II portion studying giving vincristine sulfate together with topotecan hydrochloride, and cyclophosphamide to see how well it works compared with giving vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. Drugs used in chemotherapy, such as vincristine sulfate, topotecan hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop tumor growth by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

Conditions

Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (2)

• The Occurrence of Limiting Toxicity in an Eligible and Evaluable Patient.

  Limiting toxicity defined as Any Grade IV hematological toxicities lasting longer than 7 days, myelosuppression causing delays \> 14 days in delivery of therapy, \> Grade 3 thromboembolic events, \> Grade 3 bleeding events, \> Grade 2 hypertension, \> Grade 2 proteinuria.

  First 2 courses (42 days) of therapy

• Time to Disease Progression in Patients Receiving VTC With or Without Bevacizumab

  Time from enrollment to disease progression, death, second malignant neoplasm, or last patient follow-up whichever occurs first. Patients who experience disease progression, death or second malignant neoplasm will be considered to have experienced an event; otherwise the patient will be considered censored at last follow-up.

  Maximum of 5 years after enrollment

Study Arms (3)

Arm I (Feasibility assessment of VTCB)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide; Biological: bevacizumab

Arm II (VTCB)

EXPERIMENTAL

Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.

Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide; Biological: bevacizumab

Arm III (CTC)

ACTIVE COMPARATOR

Patients receive vincristine, topotecan hydrochloride, and cyclophosphamide as in arm I.

Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide

Interventions

topotecan hydrochloride DRUG

Given IV

Also known as: hycamptamine, Hycamtin, SKF S-104864-A, TOPO

Arm I (Feasibility assessment of VTCB); Arm II (VTCB); Arm III (CTC)

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Arm I (Feasibility assessment of VTCB); Arm II (VTCB); Arm III (CTC)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I (Feasibility assessment of VTCB); Arm II (VTCB); Arm III (CTC)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm I (Feasibility assessment of VTCB); Arm II (VTCB)

Eligibility Criteria

• Age: 1 Year - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ALT =\< 5 times ULN for age
• Urine protein: creatinine ratio =\< 0.5 OR 24-hour urine protein \< 1,000 mg
• At least 6 weeks since other prior substantial bone marrow radiation
• At least 28 days since prior major surgical procedures (e.g., resection of tumor, laparotomy, thoracotomy, or open biopsy)
• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
• At least 2 weeks since prior local palliative radiotherapy (e.g., small port)
• Diagnosis of extracranial Ewing sarcoma or primitive neuroectodermal tumor of bone or soft tissue meeting 1 of the following criteria: I) a first recurrence of localized disease; II) a first recurrence of initially metastatic disease; III) disease refractory to initial conventional therapy
• Patients must have RECIST-measurable disease documented by clinical, radiographic, or histological criteria
• Patients who do not have measurable disease (e.g., bone scan-determined metastatic disease only) remain eligible for the study and will be evaluable for disease-free progression
• Karnofsky performance status (PS) 50-100% (\> 16 years of age) OR Lansky PS 50-100% (=\< 16 years of age )
• Life expectancy \>= 8 weeks
• Absolute neutrophil count \>= 1,000/μL
• NOTE: Patients with tumor metastatic to bone marrow are permitted to receive transfusions to maintain hemoglobin and platelet counts. These patients will not be evaluable for hematologic toxicity. Patients who are refractory to platelet infusions (i.e., unable to maintain platelet counts \> 75,000/μL) and have marrow involvement and platelet counts \< 75,000/μL are not eligible
• Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
• At least 1 week since prior therapy with a biologic agent or growth factor

You may not qualify if:

• Radiological or clinical evidence for parenchymal brain metastases or neuro axis involvement
• Documented, chronic nonhealing wound, ulcer, or significant traumatic injury (those with bone fractures, including pathological fractures, or requiring surgical intervention) within the past 28 days
• Other bone complications
• Deep venous thrombosis (including pulmonary embolism) within the past 3 months
• Recent (i.e., within 6 months) arterial thromboembolic events, including transient ischemic attack or cerebrovascular accident
• History of myocardial infarction, severe or unstable angina, or peripheral vascular disease Prior bevacizumab
• Radiotherapy or surgery for local control of recurrent disease concurrently with bevacizumab (bevacizumab must be held if radiotherapy or surgery is required)
• Radiotherapy to localized painful lesions is allowed, provided \>= 1 measurable lesion is not irradiated
• Radiotherapy for local metastatic tumor control allowed after the first 2 courses of therapy
• Other cancer chemotherapy or immunomodulating agents
• Steroid use is allowed
• Prior allogeneic SCT

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Children's Oncology Group

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Topotecan; trioctyl phosphine oxide; Vincristine; Cyclophosphamide; Bevacizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

In preparing to re-open for randomized enrollment in November, 2008 the study committee was asked to amend the study and the decision was made to close AEWS0521 for administrative purpose.

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Patrick Leavey, MD

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2007
• First Posted: August 15, 2007
• Study Start: February 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: January 1, 2010
• Last Updated: September 2, 2014
• Results First Posted: September 2, 2014

Record last verified: 2014-07

Locations

US (1)