Ignite Creation Date:
2024-05-06 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05691478
Status:
SUSPENDED
Last Update Posted:
2024-07-11
First Post:
2023-01-18
Brief Title:
A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Feasibility and Randomized Phase 23 Study of the VEFGR2MET Inhibitor Cabozantinib in Combination With Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma
Status:
SUSPENDED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Scheduled Interim Monitoring
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IIIII trial tests the safety side effects and best dose of the drug cabozantinib in combination with standard chemotherapy and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways This may help slow the growth of tumor cells The drugs used in standard chemotherapy for this trial are methotrexate doxorubicin and cisplatin MAP Methotrexate stops cells from making DNA and may kill tumor cells It is a type of antimetabolite Doxorubicin is in a class of medications called anthracyclines It works by slowing or stopping the growth of tumor cells in the body Cisplatin is in a class of medications known as platinum-containing compounds It works by killing stopping or slowing the growth of tumor cells Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma
Detailed Description:
PRIMARY OBJECTIVES
I To determine the feasibility of adding cabozantinib S-malate cabozantinib to standard MAP high dose methotrexate doxorubicin hydrochloride doxorubicin and cisplatin chemotherapy in patients with newly diagnosed metastatic osteosarcoma with a resectable primary tumor
II To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival EFS than MAP chemotherapy alone in patients with localized resectable osteosarcoma
III To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival EFS than MAP chemotherapy alone in patients with metastatic pelvic and unresectable osteosarcoma
SECONDARY OBJECTIVES
I To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival OS than MAP chemotherapy alone in patients with localized resectable osteosarcoma
II To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival OS than MAP chemotherapy alone in patients with metastatic pelvic and unresectable osteosarcoma
EXPLORATORY OBJECTIVES
I To determine the rate of good histologic response 90 of resected primary tumor specimens following neoadjuvant chemotherapy with MAP plus cabozantinib and compare with response rates for MAP chemotherapy alone
II To describe the toxicities of the addition of cabozantinib to MAP chemotherapy in patients with newly diagnosed osteosarcoma
III To describe frequency of application of local control methods surgery hypofractionated stereotactic body radiotherapy or radiofrequency ablation for extrapulmonary metastatic osteosarcoma
IV To compare total cumulative delivered doses of MAP chemotherapy agents between standard and experimental arms across multiple phases of therapy
V To assess the pharmacokinetics of cabozantinib when administered concomitantly with standard chemotherapy agents during feasibility
VI To collect pulmonary metastatic lesions paired primary tumor tissue and serial blood samples for tumor profiling liquid biopsies and future testing of correlative biology studies
OUTLINE This is a dose-escalation study of cabozantinib Feasibility Phase followed by a randomized phase IIIII study Efficacy Phase
FEASIBILITY PHASE Patients receive cabozantinib orally PO methotrexate intravenously IV doxorubicin IV and cisplatin IV for two 35-day induction cycles Patients are then considered for appropriate local control Then they receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle followed by cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle and cabozantinib PO methotrexate IV and doxorubicin IV for two 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
EFFICACY PHASE Patients with standard risk osteosarcoma are randomized to Arm A or Arm B Patients with high risk osteosarcoma are randomized to Arm C or Arm D
ARM A Standard risk patients receive methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles
ARM B Standard risk patients receive cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day consolidation cycles and cabozantinib PO methotrexate IV and doxorubicin IV for two additional 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
ARM C High risk patients receive methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles
ARM D High risk patients receive cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle followed by cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle and cabozantinib PO methotrexate IV and doxorubicin IV for two additional 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
All patients also undergo X-ray computed tomography CT magnetic resonance imaging MRI and positron emission tomography PET or bone scintigraphy at diagnosis and additonal time points throughout the trial All patients also undergo collection of blood samples during screening and on study
I To determine the feasibility of adding cabozantinib S-malate cabozantinib to standard MAP high dose methotrexate doxorubicin hydrochloride doxorubicin and cisplatin chemotherapy in patients with newly diagnosed metastatic osteosarcoma with a resectable primary tumor
II To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival EFS than MAP chemotherapy alone in patients with localized resectable osteosarcoma
III To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival EFS than MAP chemotherapy alone in patients with metastatic pelvic and unresectable osteosarcoma
SECONDARY OBJECTIVES
I To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival OS than MAP chemotherapy alone in patients with localized resectable osteosarcoma
II To determine whether MAP chemotherapy plus cabozantinib results in more favorable overall survival OS than MAP chemotherapy alone in patients with metastatic pelvic and unresectable osteosarcoma
EXPLORATORY OBJECTIVES
I To determine the rate of good histologic response 90 of resected primary tumor specimens following neoadjuvant chemotherapy with MAP plus cabozantinib and compare with response rates for MAP chemotherapy alone
II To describe the toxicities of the addition of cabozantinib to MAP chemotherapy in patients with newly diagnosed osteosarcoma
III To describe frequency of application of local control methods surgery hypofractionated stereotactic body radiotherapy or radiofrequency ablation for extrapulmonary metastatic osteosarcoma
IV To compare total cumulative delivered doses of MAP chemotherapy agents between standard and experimental arms across multiple phases of therapy
V To assess the pharmacokinetics of cabozantinib when administered concomitantly with standard chemotherapy agents during feasibility
VI To collect pulmonary metastatic lesions paired primary tumor tissue and serial blood samples for tumor profiling liquid biopsies and future testing of correlative biology studies
OUTLINE This is a dose-escalation study of cabozantinib Feasibility Phase followed by a randomized phase IIIII study Efficacy Phase
FEASIBILITY PHASE Patients receive cabozantinib orally PO methotrexate intravenously IV doxorubicin IV and cisplatin IV for two 35-day induction cycles Patients are then considered for appropriate local control Then they receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle followed by cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle and cabozantinib PO methotrexate IV and doxorubicin IV for two 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
EFFICACY PHASE Patients with standard risk osteosarcoma are randomized to Arm A or Arm B Patients with high risk osteosarcoma are randomized to Arm C or Arm D
ARM A Standard risk patients receive methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles
ARM B Standard risk patients receive cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day consolidation cycles and cabozantinib PO methotrexate IV and doxorubicin IV for two additional 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
ARM C High risk patients receive methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles
ARM D High risk patients receive cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for two 35-day induction cycles followed by appropriate local control Patients then receive consolidation with methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle followed by cabozantinib PO methotrexate IV doxorubicin IV and cisplatin IV for one 35-day cycle and cabozantinib PO methotrexate IV and doxorubicin IV for two additional 35-day cycles Patients then receive cabozantinib PO for six 28-day maintenance cycles
All patients also undergo X-ray computed tomography CT magnetic resonance imaging MRI and positron emission tomography PET or bone scintigraphy at diagnosis and additonal time points throughout the trial All patients also undergo collection of blood samples during screening and on study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA180886 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180886 |
| NCI-2022-08567 | REGISTRY | None | None |
| AOST2032 | OTHER | None | None |
| AOST2032 | OTHER | None | None |