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Pemetrexed Disodium and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01450384
Recruitment Status : Completed
First Posted : October 12, 2011
Last Update Posted : February 23, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Virginia Commonwealth University

Tracking Information
First Submitted Date  ICMJE September 30, 2011
First Posted Date  ICMJE October 12, 2011
Last Update Posted Date February 23, 2016
Study Start Date  ICMJE October 2011
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2014)
Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate [ Time Frame: At least 4 weeks ]
Maximum doses of pemetrexed and sorafenib, which, when administered in combination are determined to be tolerable and will be tested in a Phase 2 trial for efficacy.
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2011)
Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate [ Time Frame: 2 years ]
Maximum doses of pemetrexed and sorafenib, which, when administered in combination are determined to be tolerable and will be tested in a Phase 2 trial for efficacy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2014)
  • Number of subjects in whom study treatment produces antitumor effects of the combination [ Time Frame: Up to 4 years ]
    Tumor masses will be evaluated for response according to the Response Evaluation Criteria In Solid Tumors (RECIST) Criteria v 1.1
  • Number of biopsy specimens that successfully stain for Beclin1 [ Time Frame: Baseline up to 4 weeks ]
    Determine if biopsy specimens can be stained and analyzed for Beclin1. Assessed by use of a repeated measure analysis through a linear mixed model, as well as an ordinal regression analysis.
  • Number of biopsy specimens that can be analyzed for PDGFRb expression [ Time Frame: Baseline up to 4 weeks ]
    Assessed by use of a repeated measure analysis through a linear mixed model, as well as an ordinal regression analysis.
  • Analysis of pTEN expression in biopsy specimens [ Time Frame: Baseline up to 4 weeks ]
    Assessed by use of a repeated measure analysis through a linear mixed model, as well as an ordinal regression analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2011)
  • Number of subjects in whom study treatment produces antitumor effects of the combination [ Time Frame: 2 years ]
  • Number of biopsy specimens that successfully stain for Beclin1 [ Time Frame: 2 years ]
    Determine if biopsy specimens can be stained and analyzed for Beclin1
  • Number of biopsy specimens that can be analyzed for PDGFRb expression [ Time Frame: 2 years ]
  • Analysis of pTEN expression in biopsy specimens [ Time Frame: 2 years ]
  • Analysis of ZMP levels (marker of AICART inhibition) in peripheral blood mononuclear cells [ Time Frame: 2 years ]
  • Analysis of ZMP levels in CTCs, collected before and after pemetrexed administration [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pemetrexed Disodium and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors
Official Title  ICMJE Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy
Brief Summary This phase I trial studies the side effects and best dose of giving pemetrexed disodium and sorafenib tosylate together in treating patients with advanced solid tumors. Pemetrexed disodium and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of solid tumors by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib tosylate may kill more tumor cells.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine doses for the combination of pemetrexed (pemetrexed disodium) with sorafenib (sorafenib tosylate) appropriate for Phase II study.

SECONDARY OBJECTIVES:

I. To evaluate the safety, tolerance, and toxicity of the combination of pemetrexed and sorafenib.

II. To observe antitumor effects of the combination.

OUTLINE: This is a dose-escalation study of pemetrexed disodium and sorafenib tosylate.

Patients receive pemetrexed disodium intravenously (IV) on day 1 every 2 weeks and sorafenib tosylate orally (PO) twice daily (BID) on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor
Intervention  ICMJE
  • Drug: sorafenib tosylate
    Given PO
    Other Names:
    • BAY 43-9006
    • BAY 43-9006 Tosylate Salt
    • BAY 54-9085
    • Nexavar
    • SFN
  • Drug: pemetrexed disodium
    Given IV
    Other Names:
    • ALIMTA
    • LY231514
    • MTA
  • Other: laboratory biomarker analysis
    Correlative studies
  • Procedure: biopsy
    Optional correlative studies
    Other Name: biopsies
Study Arms  ICMJE Experimental: Treatment (enzyme inhibitor therapy, antiangiogenesis)
Patients receive pemetrexed disodium IV on day 1 every 2 weeks and sorafenib tosylate PO BID for 4 weeks on days 1-5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: sorafenib tosylate
  • Drug: pemetrexed disodium
  • Other: laboratory biomarker analysis
  • Procedure: biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 6, 2015)
37
Original Estimated Enrollment  ICMJE
 (submitted: October 11, 2011)
83
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Advanced solid tumor malignancy for which there is no potentially curative treatment; there is no limit to the number of prior lines of therapy
  • Performance status Eastern Cooperative Oncology Group (ECOG) equal or less than 1
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper institutional limit (ULN)
  • Total bilirubin =< 1.5 ULN
  • Creatinine clearance (CrCl) >= 45 mL/min as measured by the standard Cockcroft-Gault equation
  • International normalized ratio (INR) =< 1.5 (if not due to anticoagulants)
  • White blood cell count (WBC) >= 3,000 cells/mm3
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm3
  • Platelets >= 100,000 cells/mm3
  • Hemoglobin (Hgb) >= 8.5 g/dL
  • Prior toxicities are allowed as long as they are stable and would not interfere with study drug toxicity assessment
  • Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) (v 1.1)
  • Ability to understand and the willingness to sign a written informed consent document; a signed informed consent must be obtained prior to any study specific procedures
  • Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment; women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation; men must agree to use a medically accepted form of birth control for 2 months following completion of study treatment

Exclusion Criteria:

  • Any investigational agent within 4 weeks of first dose of study treatment
  • Unwillingness or inability to take folic acid, vitamin B12, or dexamethasone
  • Known or presumed intolerance of pemetrexed or sorafenib; unable to swallow medication; suspected malabsorption
  • Active illicit substance or alcohol abuse
  • Contraindication to antiangiogenic agents, including:
  • Pulmonary hemorrhage/bleeding event >= Grade 2 within 4 weeks or less prior to the first dose of study drug
  • Any other hemorrhage/bleeding event >= Grade 3 within 4 weeks or less prior to the first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Thrombolic or embolic events such as a myocardial infarction, cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring anti-arrhythmic therapy
  • Systolic blood pressure > 160 mmHg or diastolic pressure > 100 mmHg despite optimal medical management
  • Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5 day period
  • Serious uncontrolled infection > Common Terminology Criteria for Adverse Events (CTCAE) (v 4) grade 2
  • Peripheral motor or sensory neuropathy>CTCAE (v4) grade 2
  • Uncontrolled metastatic brain disease
  • Serum B12 or folate levels below the institution's lower limit of normal. Patients may begin B12/folic acid supplementation and can be reconsidered for study once levels meet the eligibility requirements
  • Administration of non-steroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to pemetrexed dosing (note: if a candidate routinely takes NSAIDs prior to enrollment, consider transition to alternate non-NSAID for duration of study treatment, if possible).
  • Other condition(s) that in the opinion of the investigator might compromise the objectives of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01450384
Other Study ID Numbers  ICMJE MCC-13874
NCI-2011-03035 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA016059 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Andrew Poklepovic Massey Cancer Center
PRS Account Virginia Commonwealth University
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP