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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

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

Treatments: Drug: sunitinib malate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00474994

P30CA008748 (U.S. NIH Grant/Contract)

MSKCC-07054

PFIZER-MSKCC-07054

07-054

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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53 participants in 3 patient groups

Group A

Experimental group

Description:

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.

Treatment:

Drug: sunitinib malate

Group B

Experimental group

Description:

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.

Treatment:

Drug: sunitinib malate

Group C

Experimental group

Description:

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.

Treatment:

Drug: sunitinib malate