Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

A Phase II Study of BAY 43-9006 in Advanced/Recurrent Uterine Carcinoma/Carcinosarcoma

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. This phase II trial is studying how well sorafenib works in treating patients with advanced or recurrent uterine cancer.

Study Overview

• Status: Completed
• Conditions: Uterine Carcinosarcoma; Recurrent Uterine Sarcoma; Stage III Uterine Sarcoma; Stage IV Uterine Sarcoma
• Intervention / Treatment: Drug: sorafenib tosylate

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with advanced or recurrent uterine cancer treated with sorafenib.

II. Determine the toxic effects of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine progression-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (carcinoma vs carcinosarcoma).

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

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario At Kingston General Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90033-0804
      • University of Southern California
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Springfield, Illinois, United States, 60702
      • Central Illinois Hematology Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• No prior sorafenib

• Histologically or cytologically confirmed uterine carcinoma or carcinosarcoma:

  • Advanced or recurrent disease
  • Not amenable to curative surgery or radiotherapy

• Measurable disease:

  • At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• Tumor tissue block must be available
• No known brain metastases

• Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

• Hematopoietic:

  • Absolute neutrophil count >= 1,500/mm3
  • Platelet count >= 100,000/mm3
  • No bleeding diathesis

• Hepatic:

  • Bilirubin normal
  • AST and ALT =< 2.5 times upper limit of normal

• Renal:

  • Creatinine =< 1.5 mg/dL OR
  • Creatinine clearance >= 60 mL/min

• Cardiovascular:

  • No uncontrolled hypertension, defined by 1 of the following:

    • Blood pressure > 150/100 mm Hg
    • Currently taking > 1 antihypertensive agent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No swallowing dysfunction that would preclude study drug ingestion
• No other uncontrolled illness
• Prior biological response modifier therapy allowed
• No prior antiangiogenesis therapy
• No prior MAPK-signaling agents
• No prior vascular endothelial growth factor receptor (VEGFR) inhibitors
• No more than 1 prior chemotherapy regimen
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• Prior hormonal therapy allowed
• Prior radiotherapy allowed provided the only site of measurable disease was not located within the radiation port OR disease has progressed since completion of therapy
• Recovered from all prior therapy

• Concurrent warfarin allowed provided all of the following are true:

  • Patient is therapeutic on a stable warfarin dose
  • INR target range =< 3
  • Patient is monitored with weekly INR testing
  • No active bleeding or pathological condition that carries a high bleeding risk
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• More than 4 weeks since prior radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Overall Response Rate	Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive.	Up to 5 years
Progression Free Survival	Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions.	Up to 5 years
Duration of Response	Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gini Fleming, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: October 12, 2005
• First Submitted That Met QC Criteria: October 12, 2005
• First Posted (Estimate): October 13, 2005

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neoplasms, Complex and Mixed; Sarcoma; Recurrence; Carcinosarcoma; Mixed Tumor, Mullerian; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2009-00068; N01CM62203 (U.S. NIH Grant/Contract); 13572A; CDR0000445181