Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

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

Summary: 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: 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.

Eligibility: 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)

Relevance to patient case: not relevant