Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)
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Purpose
This phase II trial is studying how well sorafenib works in treating patients with soft tissue sarcoma. Sorafenib may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and blocking some of the enzymes needed for tumor cell growth
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Metastatic Osteosarcoma Recurrent Adult Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Osteosarcoma Stage I Adult Soft Tissue Sarcoma Stage II Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma |
Drug: sorafenib tosylate Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis Other: pharmacological study Procedure: computed tomography Procedure: dynamic contrast-enhanced magnetic resonance imaging |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Clinical and Correlative Study of BAY 43-9006 (Sorafenib) IND 69,896 in Sarcoma |
- Change in FDG uptake (SUVmax) [ Time Frame: Baseline to up to 1 month post-treatment ] [ Designated as safety issue: No ]Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
- Change in IFP [ Time Frame: Baseline to up to 1 month post-treatment ] [ Designated as safety issue: No ]Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
- Change in CEC/WBC [ Time Frame: Baseline to up to 1 month post-treatment ] [ Designated as safety issue: No ]Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
- Change in pericyte coverage of endothelial cells (alpha-SMA) [ Time Frame: Baseline to up to 1 month post-treatment ] [ Designated as safety issue: No ]Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
- Clinical benefit as measured by 50% reduction in IFP [ Time Frame: Baseline to surgery ] [ Designated as safety issue: No ]
- Clinical benefit, measured by any reduction in tumor dimensions on CT scan as measured by RECIST criteria [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Incidence of adverse events [ Time Frame: Up to 1 month ] [ Designated as safety issue: Yes ]
| Enrollment: | 24 |
| Study Start Date: | June 2006 |
| Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
|
Drug: sorafenib tosylate
Given PO
Other Names:
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: computed tomography
Correlative studies
Other Name: tomography, computed
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Correlative studies
Other Name: DCE-MRI
|
|
Experimental: Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
|
Drug: sorafenib tosylate
Given PO
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: computed tomography
Correlative studies
Other Name: tomography, computed
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Correlative studies
Other Name: DCE-MRI
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine if the combined VEGF-R2/PDGFR beta inhibitor BAY 43-9006/ sorafenib can decrease interstitial fluid pressure (IFP) in soft tissue sarcomas.
II. To investigate the effects of BAY 43-9006/sorafenib on tumor blood flow, circulating endothelial cells, vascular density and pericyte coverage.
III. To characterize the pharmacokinetics of BAY 43-9006/sorafenib in sarcoma patients.
SECONDARY OBJECTIVES:
I. To describe any preliminary evidence of anti-tumor activity. II. Assess whether there are any significant relationships between systemic drug exposure and drug-related toxicity or biological effect.
OUTLINE: This is a multicenter study. Patients are assigned to one of two groups (group 1 closed to accrual as of 5/30/07).
GROUP I (SARCOMAS OF THE EXTREMITY) (CLOSED TO ACCRUAL AS OF 5/30/07): Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
GROUP II (METASTATIC OR INOPERABLE SARCOMAS): Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
In both groups, blood samples are drawn periodically for pharmacological studies.
After completion of study therapy, patients are followed monthly until all study-related toxicities are resolved and then at the discretion of the investigator.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
There are two groups of patients eligible for this study; treatment group 1 consists of patients with extremity sarcomas other than potentially curable osteosarcoma or Ewing's sarcoma who are candidates for potentially curative surgery; treatment group 2 consists of patients with metastatic or inoperable sarcoma, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies; patients must have at least one site of measurable disease by radiologic imaging techniques; patients must have at least one palpable tumor mass with no overlying viscera which is amenable to biopsy; the tumor mass should be approximately 2 cm or greater in diameter; patients with smaller palpable tumors are eligible if participation is approved by the treating surgeon after discussion with the study chairperson
- As of 5/30/07, no subjects will accrue to Treatment Group I
- Life expectancy >= 2 months
- ECOG performance status =< 2
- Pretreatment laboratory data, obtained within 14 days of study entry, must meet the following criteria:
- ANC >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- SGOT =< 2.5-times the upper limit of normal (ULN)
- SGPT =< 2.5-times ULN
- Total Bilirubin =< ULN
- Serum creatinine =< 1.5-times ULN
- >= 3 weeks since major surgery unrelated to study disease (sarcoma)
- >= 3 weeks since chemotherapy or radiation therapy (6 weeks for nitrosourea or mitomycin C chemotherapy)
- No prior treatment with sorafenib (BAY 43-9006) or specific inhibitors of MAPK kinase pathways are permitted; a previously irradiated tumor site cannot be used for clinical or correlative measurements, although irradiation to sites other than a measurable site is permitted; there are no limitations on the extent or type of prior therapy received by the patient other than the time intervals indicated in the above and demonstrating complete recovery from any adverse effects associated by satisfying all relevant eligibility criteria
- Patients who are on warfarin anticoagulation are allowed to participate as long as they are converted to a low molecular weight heparin (e.g. lovenox) from study entry until at least day 56
- Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential (age < 50, LMP < 12 months ago) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to receiving the study medication; BAY43-9006 has antiproliferative effects, which may be harmful to the developing fetus or nursing infant
- Fertile males and females must use adequate contraception
- Signed informed consent
Exclusion Criteria:
- Ewing's sarcoma or osteosarcoma that is potentially curable with surgery, chemotherapy, and/or radiation therapy
- Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirements for steroids, or enzyme-inducing anti-convulsant agents, or clinical symptoms of/from brain metastases; patients with treated and/or stable brain metastasis who are asymptomatic can be enrolled, if otherwise eligible
- Any uncontrolled serious medical or psychiatric illness; particular note is given to uncontrolled hypertension (discretion left to investigators) and significant proteinuria > 1 gm/24 hr (does not require quantitation in absence of clinical indication)
- Patients receiving other investigational agents
- HIV patients receiving combination anti-retroviral therapy are excluded because of potential pharmacokinetic interactions
Contacts and Locations More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00330421 History of Changes |
| Other Study ID Numbers: | NCI-2012-03122, 05-033, U01CA062490 |
| Study First Received: | May 25, 2006 |
| Last Updated: | April 26, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Osteosarcoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Sarcoma Sarcoma, Ewing's Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms |
Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Glandular and Epithelial Sorafenib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013