A Phase 2 interventional study of Epirubicin Hydrochloride and External Beam Radiation Therapy in Pleomorphic Rhabdomyosarcoma, Stage IIB Adult Soft Tissue Sarcoma AJCC v7 and Stage III Adult Soft Tissue Sarcoma AJCC v7, sponsored by OHSU Knight Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-21.
Sponsored by OHSU Knight Cancer Institute · Phase 2, Interventional, and Treatment
This phase II trial studies how well sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery work in treating patients with high-risk stage IIB-IV soft tissue sarcoma. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin hydrochloride and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery may be an effective treatment for soft tissue sarcoma.
PRIMARY OBJECTIVES:
I. To determine the pathologic response rate (>= 95% necrosis) after preoperative treatment with sorafenib (sorafenib tosylate), epirubicin (epirubicin hydrochloride), ifosfamide, and hypofractionated radiation for high risk soft tissue sarcomas of the extremities or body wall.
SECONDARY OBJECTIVES:
I. To further characterize the safety of sorafenib plus chemoradiotherapy, including wound complication rate.
II. To estimate time-to-event rates, including overall survival, overall disease-free survival, distant disease-free survival, and local disease-free survival in patients with high risk soft tissue sarcomas of the extremities or body wall treated with preoperative sorafenib plus chemoradiotherapy and postoperative sorafenib plus chemotherapy.
OUTLINE:
Patients receive sorafenib tosylate orally (PO) once daily (QD) on days 1-71 and 85-155, epirubicin hydrochloride intravenously (IV) over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo external beam radiation therapy (EBRT) on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.
After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.
1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.
This study's enrollment of 20 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →OHSU Knight Cancer Institute is the lead sponsor of 242 studies on the registry; 45 are open to participants now.
Of its 27 completed or terminated interventional studies of FDA-regulated products, 15 (56%) have results posted.
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American Joint Committee on Cancer (AJCC) (7th edition) stage IIb, III, or IV patients planned for resection of the primary tumor
Exclusion Criteria:
Patients receive sorafenib tosylate PO QD on days 1-71 and 85-155, epirubicin hydrochloride IV over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo EBRT on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.
Drug: Epirubicin Hydrochloride · Radiation: External Beam Radiation Therapy · Drug: Ifosfamide · Other: Laboratory Biomarker Analysis · Drug: Sorafenib Tosylate · Procedure: Therapeutic Conventional Surgery
Given IV
Also known as: Ellence, IMI-28, Pharmorubicin PFS
Undergo EBRT
Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation
Given IV
Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942
Correlative studies
Given PO
Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Undergo surgical resection
Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.
Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.
Time frame: Assessed at surgical resection
Number of Grade 3-4 Adverse Events
Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Time frame: Up to 5 years
Number of Participants With Wound Complications
Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.
Time frame: At least 120 days
Overall Survival at 2 Years
Percentage of patients alive at 2 years, Method of Kaplan-Meier used.
Time frame: Time from registration until death from any cause
Overall Disease-free Survival (Stage IIB-III Patients)
Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \\used.
Time frame: Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years
Distant Disease-free Survival (Stage IIB-III Patients)
Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.
Time frame: Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years
Number of Participants With Local Recurrence
Number of patients with local recurrence after surgical resection of the primary tumor
Time frame: Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)
| Milestone | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Started | 20 |
| Completed | 20 |
| Not completed | 0 |
Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.
| % of participants | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis. | 20 (5.7 to 43.7) |
Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
| Grade 3-4 Adverse Events | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Number of Grade 3-4 Adverse Events | 86 |
Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.
| Participants | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Number of Participants With Wound Complications | 10 |
Percentage of patients alive at 2 years, Method of Kaplan-Meier used.
| percentage of patients | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Overall Survival at 2 Years | 82 (54 to 94) |
Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \\used.
| Months | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Overall Disease-free Survival (Stage IIB-III Patients) | 13.3 (6 to NA) |
Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.
| Months | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Distant Disease-free Survival (Stage IIB-III Patients) | 16.4 (8.9 to NA) |
Number of patients with local recurrence after surgical resection of the primary tumor
| Participants | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Number of Participants With Local Recurrence | 0 |
Collected over Toxicity measure through follow up, every 4 months until patient death or withdrawal, a median of 34.5 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) | 5/20 (25%) | 18/20 (90%) | 20/20 (100%) |
| Event | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Febrile NeutropeniaBlood and lymphatic system disorders | 12/20 |
| wound infectionInfections and infestations | 7/20 |
| EncephalopathyNervous system disorders | 3/20 |
| SepsisInfections and infestations | 3/20 |
| Platelet Count DecreasedInvestigations | 2/20 |
| Catheter Related infectionInfections and infestations | 1/20 |
| ConstipationGastrointestinal disorders | 1/20 |
| DeliriumPsychiatric disorders | 1/20 |
| DiarrheaGastrointestinal disorders | 1/20 |
| enterocolitis infectiousInfections and infestations | 1/20 |
| Event | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Lymphocyte count decreasedInvestigations | 20/20 |
| Platelet count decreasedInvestigations | 20/20 |
| AnemiaBlood and lymphatic system disorders | 19/20 |
| Neutrophil Count DecreasedInvestigations | 18/20 |
| White Blood Cell DecreasedInvestigations | 18/20 |
| HypoalbuminemiaMetabolism and nutrition disorders | 16/20 |
| HypophosphatemiaMetabolism and nutrition disorders | 16/20 |
| nauseaGastrointestinal disorders | 13/20 |
| hypocalcemiaMetabolism and nutrition disorders | 12/20 |
| HypomagnesemiaMetabolism and nutrition disorders | 12/20 |
| Age, Categorical(Participants) | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 17 |
| >=65 years | 3 |
| Sex: Female, Male(Participants) | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Female | 11 |
| Male | 9 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 18 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 0 |
| White | 18 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Treatment (Sorafenib, Chemotherapy, Radiation, Surgery) |
|---|---|
| United States | 20 |
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OHSU Knight Cancer Institute