Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas

Study Overview
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Brief Summary
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RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with metastatic, locally advanced, or locally recurrent sarcomas.

Detailed Description
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OBJECTIVES: Primary Determine the response rate (complete response and partial response) in patients with metastatic, locally advanced, or locally recurrent non-gastrointestinal stromal tumor sarcomas treated with sunitinib malate. Secondary Determine the 16- and 24-week progression-free survival rate (complete response, partial response, and stable disease) in patients treated with this drug. Determine the overall survival in patients treated with this drug. Correlate clinical response with changes in soluble angiogenesis mediator levels in patients treated with this drug. Determine the tumor maximum standardized uptake values by fludeoxyglucose F 18-PET scan in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified by neoplastic subtype (vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans, chordoma, or desmoid tumors vs high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)], or other nongastrointestinal connective tissue tumors [including carcinosarcomas]). Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

Official Title
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A Multicenter Phase II Study of Continuous Dosing of Sunitinib (Sutent®, SU11248) in Non-GIST Sarcomas

Conditions
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Adult Malignant Fibrous Histiocytoma of Bone, Desmoid Tumor, Endometrial Cancer, Ovarian Cancer, Sarcoma, Small Intestine Cancer

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed connective tissue neoplasm, including any of the following neoplastic subtypes: Vascular connective tissue neoplasms Leiomyosarcoma Dermatofibrosarcoma protuberans Chordoma Desmoid tumors High-grade undifferentiated pleomorphic sarcoma (e.g., malignant fibrous histiocytoma [including myxofibrosarcoma]) Carcinosarcomas (e.g., malignant mixed Müllerian tumors) Giant hemangiomata Kaposi sarcoma Metastatic, locally advanced, or locally recurrent disease Measurable disease Tumor lesions in a previously irradiated area may be considered measurable provided there is evidence of growth that cannot be attributed to necrosis or bleeding No gastrointestinal stromal tumor sarcomas Prior standard neoadjuvant or adjuvant systemic therapy required for patients with the following diagnoses: Rhabdomyosarcoma Osteosarcoma Ewing sarcoma No untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as documented on screening CT scan or MRI PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 mg/dL PT and INR ≤ 1.5 AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 1.5 mg/dL Calcium ≤ 12 mg/dL Blood glucose < 150 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy Other malignancies allowed provided sarcoma is the primary disease requiring systemic therapy Able to swallow oral medications No other disease or illness within the past 6 months, including any of the following: Myocardial infarction Severe or unstable angina Coronary or peripheral artery bypass graft Symptomatic congestive heart failure Cerebrovascular accident or transient ischemic attack Pulmonary embolism No evidence of a bleeding diathesis No ongoing cardiac dysrhythmias > grade 2 No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan No psychiatric illness or social situation that would preclude study compliance No pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication No prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline EKG No hemorrhage ≥ grade 3 in the past 4 weeks PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior therapy No prior sunitinib malate No more than 3 prior cytotoxic chemotherapy regimens for metastatic disease Adjuvant chemotherapy for sarcoma completed > 1 year prior to study entry is not considered a line of prior treatment At least 2 weeks since prior cytotoxic chemotherapy At least 6 weeks since prior carmustine or mitomycin C At least 1 week since prior biological therapy or small molecule kinase inhibitors At least 3 weeks since prior radiotherapy (except for palliative radiotherapy to specific sites) Prior palliative radiotherapy allowed provided it is considered medically necessary and there are other target lesions to assess More than 4 weeks since prior major surgery Concurrent major surgery allowed provided study drug is stopped 2 weeks before surgery and resumed 2 weeks after surgery Concurrent palliative radiotherapy (e.g., focal radiotherapy to a bony metastasis for relieving bone pain) allowed No other concurrent investigational drugs No concurrent participation in another clinical trial No concurrent therapeutic anticoagulation (e.g., warfarin) Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided requirements for PT and INR are met No other concurrent approved or investigational anticancer agents or treatment, including chemotherapy, biological response modifier therapy, hormonal therapy, or immunotherapy Concurrent hormone replacement therapy for adrenal insufficiency allowed No concurrent antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) No concurrent rifampin, theophylline, ketoconazole, or Hypericum perforatum (St. John's wort)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans (DFSP), desmoid tumors. Sunitinib 37.5 mg daily continuously; one cycle is 28 days. Restaging: after every 2 cycles until after 6 cycles, when restaging will be decreased to once every 3 cycles. | Drug: sunitinib malate<br> <br> |
| Experimental: Group B<br>High grade undifferentiated pleomorphic sarcoma (includes the older designation malignant fibrous histiocytoma [MFH]) and other non-GIST connective tissue tumors; may include carcinosarcomas.Sunitinib 37.5 mg daily continuously; one cycle is 28 days. Restaging: after every 2 cycles until after 6 cycles, when restaging will be decreased to once every 3 cycles. | Drug: sunitinib malate<br> <br> |
| Experimental: Group C<br>Chordomas. Sunitinib 37.5 mg daily continuously; one cycle is 28 days. Restaging: after every 2 cycles until after 6 cycles, when restaging will be decreased to once every 3 cycles. | Drug: sunitinib malate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response | as assessed by RECIST criteria | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chondrosarcoma, recurrent osteosarcoma, localized adult malignant fibrous histiocytoma of bone, metastatic adult malignant fibrous histiocytoma of bone, recurrent adult malignant fibrous histiocytoma of bone, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Kaposi sarcoma, recurrent uterine sarcoma, adult leiomyosarcoma, adult malignant fibrous histiocytoma, adult rhabdomyosarcoma, dermatofibrosarcoma protuberans, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, ovarian sarcoma, uterine leiomyosarcoma, stage III uterine sarcoma, stage IV uterine sarcoma, desmoid tumor, adult angiosarcoma, recurrent adult soft tissue sarcoma, uterine carcinosarcoma, endometrial stromal sarcoma, fibrosarcomatous osteosarcoma, chondrosarcomatous osteosarcoma, adult alveolar soft-part sarcoma, adult epithelioid sarcoma, adult extraskeletal chondrosarcoma, adult extraskeletal osteosarcoma, adult fibrosarcoma, adult malignant hemangiopericytoma, adult malignant mesenchymoma, adult neurofibrosarcoma, adult synovial sarcoma, adult desmoplastic small round cell tumor, adult liposarcoma, anaplastic osteosarcoma, mixed osteosarcoma, small intestine leiomyosarcoma, osteoblastic osteosarcoma, telangiectatic osteosarcoma, classic Kaposi sarcoma, immunosuppressive treatment related Kaposi sarcoma, AIDS-related Kaposi sarcoma