S0505 Sorafenib in Treating Patients With Advanced Soft Tissue Sarcomas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00217620
First received: September 20, 2005
Last updated: May 5, 2014
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Sarcoma
Drug: sorafenib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of BAY-9006 (NSC #724772) in Advanced Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Response (Confirmed, Complete and Partial) [ Time Frame: Assessment performed every eight weeks until progression. ] [ Designated as safety issue: No ]
    Partial response (PR) is greater than or equal to 30% decrease under baseline of sum of longest diameters of all target measurable lesions; No unequivocal progression of non-measurable disease; No new lesions. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration. Stable disease does not qualify for CR, PR, Progression or Symptomatic Deterioration. Progressive disease is any one or more of the following: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Assessment inadequate is progression or symptomatic deterioration has not been documented, and one or more target measurable lesions have not been assessed or inconsistent assessment methods were used.


Secondary Outcome Measures:
  • Four-month Progression-free Survival Rate [ Time Frame: 0 - 4 months ] [ Designated as safety issue: No ]
  • Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events two weeks after starting protocol treatment and then after every cycle of treatment (1 cycle = 28 days) for the duration of protocol treatment. ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 - Severe, Grade 4 - Life-threatening, Grade 5 - Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported.


Enrollment: 51
Study Start Date: March 2006
Study Completion Date: September 2012
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sorafenib
sorafenib
Drug: sorafenib
800 mg per day, daily until progression
Other Name: BAY 43-9006

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00217620

  Show 184 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Margaret von Mehren, MD Fox Chase Cancer Center
Study Chair: George D. Demetri, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Ryan CW, von Mehren M, Rankin CJ, et al.: Phase II intergroup study of sorafenib (S) in advanced soft tissue arcomas (STS): SWOG 0505. [Abstract] J Clin Oncol 26 (Suppl 15): A-10532, 2008.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00217620     History of Changes
Other Study ID Numbers: NCI-2012-03063, S0505, U10CA032102, CDR0000442404
Study First Received: September 20, 2005
Results First Received: October 3, 2012
Last Updated: May 5, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult angiosarcoma
adult leiomyosarcoma
adult liposarcoma
adult malignant hemangiopericytoma
recurrent adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014