Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00134030
Status:
COMPLETED
Last Update Posted:
2023-06-07
First Post:
2005-08-22
Brief Title:
Combination Chemotherapy PEG-Interferon Alfa-2b and Surgery in Treating Patients With Osteosarcoma
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy
Status:
COMPLETED
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EURAMOS-1
Brief Summary:
This randomized phase III trial is studying combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma Drugs used in chemotherapy 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 Biological therapies such as PEG-interferon alfa-2b may interfere with the growth of tumor cells Giving combination chemotherapy before surgery may shrink the tumor so it can be removed Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma
Detailed Description:
PRIMARY OBJECTIVES
I Compare whether adjuvant maintenance therapy comprising doxorubicin cisplatin and high-dose methotrexate MAP alone vs MAP combined with ifosfamide and etoposide improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a poor histological response HR to neoadjuvant induction therapy comprising MAP
II Compare whether adjuvant maintenance therapy comprising MAP alone vs MAP and PEG-interferon alfa-2b improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a good HR to neoadjuvant induction therapy comprising MAP
SECONDARY OBJECTIVES
I Compare overall survival of patients treated with these regimens II Compare short- and long-term toxicity of these regimens in these patients III Compare quality of life of patients treated with these regimens IV Compare event-free survival and overall survival of patients with localized osteosarcoma treated with these regimens
V Correlate biological or clinical changes with histological response and outcomes in patients treated with these regimens
VI Determine outcomes of patients treated with these regimens
OUTLINE This is a randomized controlled multicenter study
INDUCTION THERAPY MAP weeks 1-10 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 and cisplatin IV over 4 hours on days 1 and 2 in weeks 1 and 6 Patients also receive high-dose methotrexate MTX IV over 4 hours on day 1 in weeks 4 5 9 and 10 Patients then proceed to surgery
NOTE Patients must receive 2 but 6 doses of high-dose MTX
SURGERY Patients undergo amputation or limb salvage surgery in week 11 Tumor tissue is evaluated for histological response to induction therapy Patients whose tumor is not amenable to macroscopically complete surgical resection undergo radiotherapy andor other investigational therapy off study Patients who undergo macroscopically complete surgical resection of the primary tumor or metastases AND who have no disease progression or unacceptable toxicity proceed to maintenance therapy
MAINTENANCE THERAPY Patients are assigned to 1 of 2 groups according to histological response good 10 viable tumor vs poor 10 viable tumor Patients in each group are stratified according to site of primary tumor and presence of metastases
GROUP 1 good histological response Patient are randomized to 1 of 2 treatment arms within 35 days after surgery
ARM I MAP weeks 12-29 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12 17 22 and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17 Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15 16 20 21 24 25 28 and 29
ARM II MAPifn weeks 12-104 Patients receive doxorubicin cisplatin and high-dose MTX as in arm I Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104
GROUP 2 poor histological response Patients are randomized to 1 of 2 treatment arms within 35 days after surgery
ARM I MAP weeks 12-29 Patients receive doxorubicin cisplatin and high-dose MTX as in group 1 arm I
ARM II MAPIE weeks 12-40 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12 20 28 and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28 Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15 19 23 27 31 35 39 and 40 Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16 24 and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16 24 and 32
In both groups treatment continues in the absence of disease progression or unacceptable toxicity Quality of life is assessed periodically
After completion of study treatment patients are followed every 1½-3 months for 2 years every 2-4 months for 2 years every 6 months for 6 years and then every 6-12 months thereafter Peer Reviewed and Funded or Endorsed by Cancer Research UK
I Compare whether adjuvant maintenance therapy comprising doxorubicin cisplatin and high-dose methotrexate MAP alone vs MAP combined with ifosfamide and etoposide improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a poor histological response HR to neoadjuvant induction therapy comprising MAP
II Compare whether adjuvant maintenance therapy comprising MAP alone vs MAP and PEG-interferon alfa-2b improves event-free survival of patients with resectable high-grade osteosarcoma who achieve a good HR to neoadjuvant induction therapy comprising MAP
SECONDARY OBJECTIVES
I Compare overall survival of patients treated with these regimens II Compare short- and long-term toxicity of these regimens in these patients III Compare quality of life of patients treated with these regimens IV Compare event-free survival and overall survival of patients with localized osteosarcoma treated with these regimens
V Correlate biological or clinical changes with histological response and outcomes in patients treated with these regimens
VI Determine outcomes of patients treated with these regimens
OUTLINE This is a randomized controlled multicenter study
INDUCTION THERAPY MAP weeks 1-10 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 and cisplatin IV over 4 hours on days 1 and 2 in weeks 1 and 6 Patients also receive high-dose methotrexate MTX IV over 4 hours on day 1 in weeks 4 5 9 and 10 Patients then proceed to surgery
NOTE Patients must receive 2 but 6 doses of high-dose MTX
SURGERY Patients undergo amputation or limb salvage surgery in week 11 Tumor tissue is evaluated for histological response to induction therapy Patients whose tumor is not amenable to macroscopically complete surgical resection undergo radiotherapy andor other investigational therapy off study Patients who undergo macroscopically complete surgical resection of the primary tumor or metastases AND who have no disease progression or unacceptable toxicity proceed to maintenance therapy
MAINTENANCE THERAPY Patients are assigned to 1 of 2 groups according to histological response good 10 viable tumor vs poor 10 viable tumor Patients in each group are stratified according to site of primary tumor and presence of metastases
GROUP 1 good histological response Patient are randomized to 1 of 2 treatment arms within 35 days after surgery
ARM I MAP weeks 12-29 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12 17 22 and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17 Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15 16 20 21 24 25 28 and 29
ARM II MAPifn weeks 12-104 Patients receive doxorubicin cisplatin and high-dose MTX as in arm I Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104
GROUP 2 poor histological response Patients are randomized to 1 of 2 treatment arms within 35 days after surgery
ARM I MAP weeks 12-29 Patients receive doxorubicin cisplatin and high-dose MTX as in group 1 arm I
ARM II MAPIE weeks 12-40 Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12 20 28 and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28 Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15 19 23 27 31 35 39 and 40 Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16 24 and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16 24 and 32
In both groups treatment continues in the absence of disease progression or unacceptable toxicity Quality of life is assessed periodically
After completion of study treatment patients are followed every 1½-3 months for 2 years every 2-4 months for 2 years every 6 months for 6 years and then every 6-12 months thereafter Peer Reviewed and Funded or Endorsed by Cancer Research UK
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2009-01066 | REGISTRY | None | None |
| ISRCTN67613327 | REGISTRY | None | None |
| MRC-BO08 | OTHER | None | None |
| MRC-EURAMOS1 | OTHER | None | None |
| 06-93 | OTHER | None | None |
| CDR0000438714 | OTHER | None | None |
| COG-AOST0331 | OTHER | None | None |
| EU-20530 | OTHER | None | None |
| 2004-000242-20 | EUDRACT_NUMBER | None | None |
| AOST0331 | OTHER | None | None |
| AOST0331 | OTHER | None | None |
| U10CA180886 | NIH | None | None |