S0505 Sorafenib in Treating Patients With Advanced Soft Tissue Sarcomas

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Sarcoma

Treatments: Drug: sorafenib

Study type: Interventional

Funder types: NIH

Identifiers

NCT00217620

S0505 (Other Identifier)

NCI-2012-03063

CDR0000442404 (Registry Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Sorafenib 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 sorafenib works in treating patients with advanced soft tissue sarcomas.

Full description

OBJECTIVES:

• Determine the objective response rate (confirmed, complete, and partial) in patients with advanced soft tissue sarcomas treated with sorafenib.
• Determine the 4-month progression-free survival rate in patients treated with this drug.
• Determine the frequency and severity of adverse events in patients treated with this drug.

OTHER OBJECTIVES (if funding permits):

• Correlate, preliminarily, a decrease in standard uptake variable (SUV) of target lesions by positron-emission tomography scan at 4 weeks with response in patients treated with this drug.
• Correlate, preliminarily, the phosphorylation status of KIT, PDGFR, VEGFR, and the raf/mek/erk pathway with response in patients treated with this drug.
• Correlate, preliminarily, the most common B-raf kinase mutation with response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (leiomyosarcoma vs liposarcoma vs angiosarcoma, hemangiosarcoma, or hemangiopericytoma).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 8 weeks until disease progression and then every 6 months for 2 years and annually for up to 3 years.

PROJECTED ACCRUAL: A total of 45-75 patients (15-25 per stratum) will be accrued for this study within 15-38 months.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed soft tissue sarcoma of 1 of the following histologies:

  • Angiosarcoma, cutaneous or visceral
  • Malignant hemangiosarcoma
  • Malignant hemangiopericytoma
  • Grade 3-4 leiomyosarcoma
  • Grade 3-4 liposarcoma

• Must have evidence of unresectable residual disease, metastatic disease, or recurrent disease by radiography

• Measurable disease by x-ray, scans, or physical examination

• Archived paraffin-embedded tumor sections available

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases)
• Bilirubin normal (≤ 2.5 times ULN if due to liver metastases)
• PT, PTT, and INR normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No history of thromboembolic disease
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Able to swallow oral medication
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 28 days since prior chemotherapy (42 days for carmustine or mitomycin) and recovered
• Prior adjuvant chemotherapy allowed
• No more than 1 prior chemotherapy regimen for metastatic disease

Endocrine therapy

• Not specified

Radiotherapy

• At least 28 days since prior radiotherapy and recovered

  • Must have evidence of disease progression within, or measurable disease outside of, the radiation field after completion of radiotherapy

Surgery

• At least 28 days since prior major surgery and recovered

Other

• No prior sorafenib

• No prior inhibitor of VEGFR or MAPK pathway

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

• No concurrent therapeutic anticoagulation

• No concurrent administration of any of the following medications:

  • Rifampin

  • Hypericum perforatum (St. John's wort)

  • Cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following:

    • Phenytoin
    • Carbamazepine
    • Phenobarbital

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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51 participants in 1 patient group

sorafenib

Experimental group

Description:

sorafenib

Treatment:

Drug: sorafenib