AzTrials
AzTrials

Ewing Sarcoma of BonePhase 2NCT00516295

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

A Phase 2 study testing topotecan hydrochloride, vincristine sulfate and cyclophosphamide in people with Ewing Sarcoma of Bone and Extraosseous Ewing Sarcoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 29 years
What is being tested?
topotecan hydrochloride, vincristine sulfate and cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
Feb 2008to Jan 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 37Show fewer
  • 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
  • Patients must have histological verification of the malignancy at original diagnosis
  • Histological confirmation of relapse is highly recommended but not mandatory
  • Prior initial therapy with topotecan hydrochloride is allowed as long as > 2 years have elapsed since the initial diagnosis of Ewing sarcoma
  • Prior therapy with cyclophosphamide or vincristine is allowed
  • Minor surgical procedures (e.g., biopsies) for limited purposes of tissue retrieval allowed
  • Minor procedures include indwelling IV catheter placement and needle biopsy for diagnostic purposes
  • For minor surgeries, patients should not receive the first planned dose of bevacizumab until the wound is healed and 7 days have elapsed
  • At least 6 months since prior craniospinal radiotherapy or radiotherapy to >= 50% of the pelvis
  • At least 3 months since prior autologous stem cell transplantation (SCT)
  • Platelet count >= 75,000/μL (transfusion independent)
  • Hemoglobin >= 8.0 g/dL (may receive RBC transfusions)
  • Direct bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • Creatinine clearance or radioisotope GFR >= 70 mL/min OR serum creatinine normal for age
  • Hypertension must be well controlled on stable doses of medication for >= 2 weeks prior to enrollment
  • Negative pregnancy test
  • Female patients who are lactating must agree to stop breast-feeding
  • II) The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • Shortening fraction > 28% OR ejection fraction > 50%
  • Recovered from any prior surgical procedure
  • Sexually active patients of childbearing potential must agree to use effective contraception
  • Patients on full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 are eligible if both of these criteria are met:
  • I) The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Oncology Group

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Randomized Phase II Study of Bevacizumab (NSC 704865) Combined With Vincristine, Topotecan and Cyclophosphamide in Patients With First Recurrent Ewing Sarcoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility of administering bevacizumab in combination with vincristine (vincristine sulfate), topotecan hydrochloride, and cyclophosphamide (VTC) to younger patients with refractory or first recurrent Ewing sarcoma.

II. To compare the progression-free survival of patients treated with VTC with bevacizumab vs VTC without bevacizumab.

SECONDARY OBJECTIVES:

  1. To estimate the response rate to 2 cycles of VTC compared to 2 cycles of VTC/bevacizumab.

II. To evaluate biological markers as related to prognosis and specifically related to angiogenesis by encouraging concurrent enrollment on the Ewing sarcoma banking studies (COG-AEWS02B1 and/or COG-AEWS07B1) and ancillary correlative endothelial cell, surrogate marker, and angiogenic gene studies.

OUTLINE: This is a single therapy feasibility study followed by a randomized controlled portion. Patients are stratified according to time to disease recurrence (< 2 years vs >= 2 years).

ARM I (Feasibility assessment of VTCB): Patients receive bevacizumab intravenously (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.

ARM II (VTCB): Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.

ARM III (VTC): Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.

After completion of study therapy, patients are followed periodically.

Being tested
topotecan hydrochloride, vincristine sulfate, cyclophosphamide, bevacizumab
Medical subject headings
Neuroectodermal Tumors, Primitive, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • topotecan hydrochlorideDrug

    Also called hycamptamine, Hycamtin, SKF S-104864-A, TOPO

    Given IV

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

Study groups in NCT00516295
Study groupRoleWhat they receive
Arm I (Feasibility assessment of VTCB)ExperimentalPatients 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.
Receives: Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide; Biological: bevacizumab
Arm II (VTCB)ExperimentalPatients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.
Receives: Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide; Biological: bevacizumab
Arm III (CTC)Active comparatorPatients receive vincristine, topotecan hydrochloride, and cyclophosphamide as in arm I.
Receives: Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: First 2 courses (42 days) of therapy

  2. 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.

    Measured: Maximum of 5 years after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2007 (estimated)
  2. Study startFeb 2008
  3. Primary completionAug 2009
  4. Study completionJan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00516295
Sponsor's protocol ID
NCI-2009-00369
Other IDs
NCI-2009-00369, AEWS0521, AEWS0521, U10CA098543
Status last verified
Jul 2014
First submitted
14 Aug 2007
Last updated
2 Sep 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing topotecan hydrochloride, vincristine sulfate and cyclophosphamide in people with Ewing Sarcoma of Bone and Extraosseous Ewing Sarcoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Occurrence of Limiting Toxicity in an Eligible and Evaluable Patient. (time frame: First 2 courses (42 days) of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00516295.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in