SarcomaPhase 3NCT00334867
Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma
A Phase 3 study testing cyclophosphamide, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Sarcoma, run by Children's Oncology Group.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages Up to 50 years
- Conditions the study is for
- Sarcoma
- What is being tested?
- cyclophosphamide, dexrazoxane hydrochloride and doxorubicin hydrochloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2005to Jan 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue
- Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules allowed
- Contralateral pleural effusions or pleural nodules are not eligible
- Tumor arising in the bony skull (extradural) are eligible
- Tumors arising in the intradural soft tissue are not eligible
- Newly diagnosed disease
- Only have had a biopsy of the primary tumor without an attempt at complete or partial resection
- Prior attempted or accomplished unplanned excision allowed provided adequate imaging was obtained prior to surgery AND resection considered incomplete and further local control required
- No evidence of metastatic disease, defined as lesions discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor
- No evidence of metastatic lung disease by CT scan
- One pulmonary nodule > 1 cm in diameter OR > 1 nodule > 0.5 cm in diameter are considered evidence of pulmonary metastasis
- Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed negative by biopsy
- Solitary nodules < 0.5 cm or multiple nodules < 0.3 cm not considered clear evidence of lung disease
- No distant nodule disease
- No esthesioneuroblastoma
PATIENT CHARACTERISTICS:
- Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients ≥ 16 years of age or Lansky PS 50-100% for patients < 16 years of age)
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Shortening fraction ≥ 27% by EKG
- Ejection fraction ≥ 50% by radionuclide angiogram
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior radiotherapy
- No prior chemotherapy
About this study
Official title: A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma
RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating Ewing's sarcoma.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and topotecan to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed localized Ewing's sarcoma.
Read the detailed description
OBJECTIVES:
Primary
- Compare the event-free and overall survival of patients with newly diagnosed localized Ewing's sarcoma treated with doxorubicin hydrochloride, cyclophosphamide, vincristine, etoposide, and ifosfamide with vs without topotecan hydrochloride.
- Compare the side effects of these regimens in these patients.
Secondary
- Evaluate initial tumor size as a prognostic factor for event-free survival of these patients.
- Evaluate histological response as a prognostic factor for event-free survival of these patients.
- Continue evaluation of biologic markers both as related to prognosis and as eventual therapeutic targets via encouraging concurrent enrollment on COG-AEWS02B1.
- Evaluate radiologic response by positron emission tomography as a prognostic factor for event-free survival.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (≤ 17 vs ≥ 18 years of age) and primary tumor site (pelvic vs nonpelvic [including extra-osseous Ewing's sarcoma]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-30, 34-36, 40-42, and 46-51; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 and doxorubicin hydrochloride as above in weeks 19 and 28; cyclophosphamide as above in weeks 19, 28, 34, 40, 46, and 49; and ifosfamide and etoposide as above in weeks 22, 25, 31, 37, and 43.
- Arm II: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-33, 37-42, and 46-48; topotecan hydrochloride as above in weeks 19, 31, and 40; cyclophosphamide IV over 30 minutes in weeks 19, 31, and 40 and IV over 1 hour in weeks 28, 37, and 46; ifosfamide and etoposide as above in weeks 22, 25, 34, 43, and 49; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 in weeks 37 and 46; and doxorubicin hydrochloride as above in weeks 28, 37, and 46.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 528 patients will be accrued for this study.
- Conditions
- Sarcoma
- Being tested
- cyclophosphamide, dexrazoxane hydrochloride, doxorubicin hydrochloride, etoposide, ifosfamide
- Keywords
- localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
- Medical subject headings
- Sarcoma, Neuroectodermal Tumors, Primitive, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Given IV
dexrazoxane hydrochlorideDrug
Given IV
Given IV
etoposideDrug
Given IV
ifosfamideDrug
Given IV
topotecan hydrochlorideDrug
Given IV
Given IV
conventional surgeryProcedure or surgery
Patients undergo surgery in week 18
radiation therapyProcedure or surgery
Patients undergo radiation therapy in week 19
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Receives: Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: radiation therapy |
| Arm II | Experimental | Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients also undergo local therapy comprising of conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Patients then proceed to combination chemotherapy. Receives: Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: topotecan hydrochloride; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
Secondary outcomes (1)
Survival form study enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2006 (estimated)
- Study startDec 2005
- Primary completionJan 2006
Why it stopped: withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mason Bond, MD, Study chair, Children's & Women's Hospital of British ColumbiaLeo Mascarenhas, MD, Study chair, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00334867
- Sponsor's protocol ID
- AEWS0531
- Other IDs
- COG-AEWS0531, CDR0000483611
- Status last verified
- Jun 2013
- First submitted
- 7 Jun 2006
- Last updated
- 28 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma
- ClinicalTrials.gov ID
- NCT00334867
- Acronym / sponsor ID
- AEWS0531
- Conditions
- Sarcoma
- Keywords
- localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2005
- Primary completion
- Jan 2006 (actual)
- First posted
- 8 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating Ewing's sarcoma.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and topotecan to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed localized Ewing's sarcoma.
Detailed description
OBJECTIVES:
Primary
- Compare the event-free and overall survival of patients with newly diagnosed localized Ewing's sarcoma treated with doxorubicin hydrochloride, cyclophosphamide, vincristine, etoposide, and ifosfamide with vs without topotecan hydrochloride.
- Compare the side effects of these regimens in these patients.
Secondary
- Evaluate initial tumor size as a prognostic factor for event-free survival of these patients.
- Evaluate histological response as a prognostic factor for event-free survival of these patients.
- Continue evaluation of biologic markers both as related to prognosis and as eventual therapeutic targets via encouraging concurrent enrollment on COG-AEWS02B1.
- Evaluate radiologic response by positron emission tomography as a prognostic factor for event-free survival.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (≤ 17 vs ≥ 18 years of age) and primary tumor site (pelvic vs nonpelvic [including extra-osseous Ewing's sarcoma]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-30, 34-36, 40-42, and 46-51; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 and doxorubicin hydrochloride as above in weeks 19 and 28; cyclophosphamide as above in weeks 19, 28, 34, 40, 46, and 49; and ifosfamide and etoposide as above in weeks 22, 25, 31, 37, and 43.
- Arm II: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients undergo local therapy comprising surgical resection in approximately week 18 and/or radiotherapy beginning in approximately week 19. Patients then receive vincristine as above in weeks 19-21, 28-33, 37-42, and 46-48; topotecan hydrochloride as above in weeks 19, 31, and 40; cyclophosphamide IV over 30 minutes in weeks 19, 31, and 40 and IV over 1 hour in weeks 28, 37, and 46; ifosfamide and etoposide as above in weeks 22, 25, 34, 43, and 49; dexrazoxane hydrochloride IV over 15 minutes on days 1 and 2 in weeks 37 and 46; and doxorubicin hydrochloride as above in weeks 28, 37, and 46.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 528 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Active comparator | Drug: cyclophosphamide, Drug: dexrazoxane hydrochloride, Drug: doxorubicin hydrochloride, Drug: etoposide, Drug: ifosfamide, Drug: vincristine sulfate, Procedure: conventional surgery, Procedure: radiation therapyPatients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. |
| Arm II | Experimental | Drug: cyclophosphamide, Drug: dexrazoxane hydrochloride, Drug: doxorubicin hydrochloride, Drug: etoposide, Drug: ifosfamide, Drug: topotecan hydrochloride, Drug: vincristine sulfate, Procedure: conventional surgery, Procedure: radiation therapyPatients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients also undergo local therapy comprising of conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Patients then proceed to combination chemotherapy. |
Who may qualify
- Ages
- Up to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideGiven IV | Drug | Arm I, Arm II |
| dexrazoxane hydrochlorideGiven IV | Drug | Arm I, Arm II |
| doxorubicin hydrochlorideGiven IV | Drug | Arm I, Arm II |
| etoposideGiven IV | Drug | Arm I, Arm II |
| ifosfamideGiven IV | Drug | Arm I, Arm II |
| topotecan hydrochlorideGiven IV | Drug | Arm II |
| vincristine sulfateGiven IV | Drug | Arm I, Arm II |
| conventional surgeryPatients undergo surgery in week 18 | Procedure or surgery | Arm I, Arm II |
| radiation therapyPatients undergo radiation therapy in week 19 | Procedure or surgery | Arm I, Arm II |
Primary outcome
Event-free survival
1 secondary outcome
Survival form study enrollment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mason Bond, MD study chair
Children's & Women's Hospital of British Columbia
Leo Mascarenhas, MD study chair
Children's Hospital Los Angeles
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cyclophosphamide, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Sarcoma, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: withdrawn, as of the sponsor's last update on 28 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Event-free survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jun 2013.