Multicenter International Study of the Feasibility and Outcomes of Carboplatin Based and Methotrexate Based Standard Treatment Regimens in Localized Osteosarcoma: A Two Arm Pragmatic Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 250
- Locations
- 1
- Primary Endpoint
- To prospectively estimate the 5-year event-free survival (EFS) rates for
Study Overview
Brief Summary
I. Study Summary
POEM-OS 2024, a prospective, two-arm pragmatic clinical trial designed to compare the effectiveness of two standard-of-care chemotherapy regimens for treating localized, surgically resectable osteosarcoma across East and Mediterranean area. The study aims to evaluate a methotrexate-based regimen (MAP) versus a carboplatin-based regimen (OS99), with the primary goal of estimating the 5-year event-free survival rates for each regimen. Secondary objectives include assessing radiologic and histopathologic response rates, 5-year overall survival, toxicity patterns, timeliness of surgical interventions, and identifying barriers to treatment.
The trial aims to enroll over 250 patients within four years, across 27 centers from 10 countries. The sample size calculation was calculated based on the primary objective of the study, which is to estimate the EFS at 3 years for each arm. To estimate a 70% EFS at a 95% confidence and a 0.05 alpha error, we need to include 165 patients in each arm for a 7% margin of error for the confidence interval. Increasing the sample size to 224 patients per arm will reduce the margin of error to 6%. The study will not centrally allocate patients to a specific treatment. Instead, one of the treatment regimens will be adopted as per the standard practice of each respective center, and therapy will then follow the respective standardized regimen.
Endpoints of the study will include measuring histopathologic response rates, overall and event-free survival rates, and the incidence and severity of adverse events, all evaluated according to international standards.
II. Objectives of the Study
The primary objective of the study is to prospectively estimate the 5-year event-free survival (EFS) rate for patients with localized, surgically resectable osteosarcoma, treated using either the OS99 regimen (carboplatin, doxorubicin, ifosfamide) or the MAP regimen (methotrexate, doxorubicin, cisplatin) following standard treatment guidelines at medical centers within the POEM region.
Secondary objectives include estimating radiologic and histopathologic response rates in patients treated with carboplatin-based and MTX-based regimens, as well as estimating the 5-year overall survival for patients receiving these treatments. Additionally, the study aims to describe patterns of toxicity, adverse events, and feasibility of timely administration associated with these regimens, and to detail the timeliness of surgical local control and any barriers encountered in patients with localized osteosarcoma.
III. Study Design and Methods
This is a prospective, two-arm pragmatic study with an emphasis on evaluating carboplatin-based and MTX-based standard-of-care therapies for patients with localized osteosarcoma in the regional context.
The recruitment period is expected to last for 4 years. The analysis of the primary endpoint, event-free survival is scheduled to start two years after the trial closes to accrual.
REDCap (Research Electronic Data Capture) software will be utilized for collecting information from participating centers.
IV. Expected Outcome
As detailed above, both MAP and Carboplatin-based regimen are being used as first-line standard of care regimens for treatment of patients with localized osteosarcoma in institutions within the POEM network, which span the Middle East, West Asia, and North Africa region. This provides the unique opportunity to evaluate prospectively, in a structured and controlled manner, the feasibility, outcome, and barriers encountered with these two regimens. The results of such a study are expected to inform the comparative efficacy of these regimens, potential barriers associated with administrating them, as well as define the characteristics that drive institutions to use of one or the other regimen.
Study Design
- Study Type
- Observational
Eligibility Criteria
- Ages
- 0.00 Year(s) to 18.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Histologically proven high-grade osteosarcoma: Patients must have a confirmed diagnosis of high-grade osteosarcoma based on histological examination.
- •Localized, resectable disease: The osteosarcoma must be localized and resectable, defined as disease that is or may become amenable to complete and potentially curative surgical resection, with no evidence of metastasis.
- •Timing of chemotherapy: Chemotherapy must commence within 30 days of completing all required clinical and metastatic workup.
- •No prior chemotherapy: Patients must not have received any previous treatment for osteosarcoma or prior chemotherapy for any other disease.
- •Organ function: Participants must have organ function within safe ranges for the chemotherapy regimens to be used in the study.
Exclusion Criteria
- •Any evidence of metastatic disease at diagnosis.
- •Unresectable disease
- •Low-grade osteosarcoma
- •Craniofacial osteosarcoma
- •Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
- •Active autoimmune disease requiring immunosuppressive treatment.
- •Known congenital immunodeficiency.
- •Baseline organ dysfunctions that make it unsafe for the patient to receive chemotherapy.
Outcomes
Primary Outcomes
To prospectively estimate the 5-year event-free survival (EFS) rates for
Time Frame: 4 years from the date of patient enrollment to the | occurrence of any of the following events: local recurrence, metastasis, disease progression, | secondary malignancy, or death from any cause.
patients with localized, surgically resectable osteosarcoma, who are treated
Time Frame: 4 years from the date of patient enrollment to the | occurrence of any of the following events: local recurrence, metastasis, disease progression, | secondary malignancy, or death from any cause.
using either OS99 regimen (carboplatin, doxorubicin, ifosfamide) or MAP
Time Frame: 4 years from the date of patient enrollment to the | occurrence of any of the following events: local recurrence, metastasis, disease progression, | secondary malignancy, or death from any cause.
regimen (methotrexate, doxorubicin, cisplatin) as per the standard treatment
Time Frame: 4 years from the date of patient enrollment to the | occurrence of any of the following events: local recurrence, metastasis, disease progression, | secondary malignancy, or death from any cause.
guidelines at medical centers within the POEM region.
Time Frame: 4 years from the date of patient enrollment to the | occurrence of any of the following events: local recurrence, metastasis, disease progression, | secondary malignancy, or death from any cause.
Secondary Outcomes
- To estimate both the radiologic response rates prior to surgery & the(histopathologic response rates post-surgery in patients with localized osteosarcoma treated with carboplatin-based & MTX-based regimens.)
- To describe the timeliness of surgical local control, & associated barriers,(in patients with localized osteosarcoma. Also the patterns of toxicity, adverse events, feasibility of timely)
Investigators
Dr Reghu K Sukumaran
TATA MEDICAL CENTER