A Phase II Open Label Basket Trial Study Using Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 406
- Primary Endpoint
- Number of Cohort 1 participants with relapse free survival (RFS) during study
Overview
Brief Summary
Ewing sarcoma (EWS) and osteosarcoma primarily affect adolescents and young adults. Common treatments include chemotherapy, surgery and radiation, however, there have been few recent advancements in the standard of care. By incorporating eflornithine (DFMO) as an additional therapy and/or maintenance therapy we hope to safely observe improved event-free survival and overall survival. There are 5 cohorts covered under this master protocol.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 0 Years to 50 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Inclusion Criteria:
- •Participants must be ≤50 years of age at enrollment.
- •Histologically confirmed Ewing sarcoma that is refractory or in first or subsequent relapse. Histological confirmation either at initial diagnosis or disease progression.
- •Relapsed: Participants that have achieved CR at any point and then relapsed following/during standard of care therapy.
- •Refractory: Participants that failed to achieve CR after standard of care therapy or having progressed during standard of care therapy.
- •Note: Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery and/or radiation therapy.
- •Extent of disease is judged by treating team to be amenable to the delivery of definitive local control (either definitive radiation, surgery, or a combination of these) at the time of study enrollment (to be completed after protocol defined Cycle 2).
- •Participants may enroll anytime during Cycle 1 or 2, prior to local control, as long as they received the same treatment during Cycle 1 and 2 as prescribed in this protocol.
- •Relapsed or refractory disease, including at least one of the following:
- •Tumor by CT or MRI
Exclusion Criteria
- •BSA of \<0.25 m2
- •Participants with current CNS disease.
- •Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.
- •Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.
- •Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
- •Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
- •Inclusion Criteria:
- •Participants must be ≤50 years of age at enrollment.
- •Infants and small children are eligible for this study, however, the treating physicians and family must be prepared to deliver adequate local control as required in this study (see BCC Surgical and Imaging Guidelines).
- •Participants with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site.
Arms & Interventions
Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control
DFMO will be administered as concurrent therapy during treatment of Ewing sarcoma. Participants completing treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a maintenance treatment for an additional 24 months.
Intervention: Eflornithine (Drug)
Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control
DFMO will be administered as concurrent therapy during treatment of Ewing sarcoma. Participants completing treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a maintenance treatment for an additional 24 months.
Intervention: Topotecan (Drug)
Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control
DFMO will be administered as concurrent therapy during treatment of Ewing sarcoma. Participants completing treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a maintenance treatment for an additional 24 months.
Intervention: Cyclophosphamide (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Eflornithine (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Cyclophosphamide (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Vincristine (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Doxorubicin (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Ifosfamide (Drug)
Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis
DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Etoposide (Drug)
Cohort 3: Osteosarcoma with relapse in the lung after resection of lung metastases
DFMO will be dosed twice daily for 730 days.
Intervention: Eflornithine (Drug)
Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Eflornithine (Drug)
Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Doxorubicin (Drug)
Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Cisplatin (Drug)
Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Methotrexate (Drug)
Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Eflornithine (Drug)
Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Doxorubicin (Drug)
Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Cisplatin (Drug)
Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control
DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.
Intervention: Methotrexate (Drug)
Outcomes
Primary Outcomes
Number of Cohort 1 participants with relapse free survival (RFS) during study
Time Frame: 2 years plus 5 years follow up
Cohort 1: To determine if relapse-free survival (RFS) in participants with relapsed or refractory Ewing sarcoma treated with multiagent chemotherapy is improved with the addition of DFMO as compared to historical outcomes of participants treated with the same multiagent chemotherapy without DFMO.
Number of Cohort 2 participants with event-free survival (EFS) during study
Time Frame: 2 years plus 5 years follow up
Cohort 2: To determine if event-free survival (EFS) in participants with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy is improved with the addition of DFMO as compared to historical outcomes of participants treated with the same multiagent chemotherapy without DFMO.
Cohort 3: Number of Cohort 3 participants at 12 months with disease control
Time Frame: 1 year plus 5 years follow up
To determine the 12-month disease control rate (DCR) in participants with completely resected recurrent osteosarcoma treated with DFMO as compared to historical controls.
Cohort 4A: Number of Cohort 4A participants with event-free survival (EFS) during study
Time Frame: 2 years plus 5 years follow up
Examine whether the addition of DFMO to post-operative chemotherapy with cisplatin, doxorubicin, and methotrexate (MAP) improves the event-free survival (EFS) for participants with osteosarcoma having localized disease with a poor histological response to 10 weeks of pre-operative chemotherapy.
Cohort 4B: Number of Cohort 4B participants with event-free survival (EFS) during study
Time Frame: 2 years plus 5 years follow up
Examine whether the addition of DFMO to post-operative chemotherapy with cisplatin, doxorubicin, and methotrexate (MAP) improves the event-free survival (EFS) for participants with osteosarcoma with metastatic disease at diagnosis (Cohort 4B).
Secondary Outcomes
- Length of time that participants experience Overall Survival (OS)(10 Years)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(2 years)
Investigators
Giselle Sholler
Beat Childhood Cancer Chair
Milton S. Hershey Medical Center