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

February 19, 2016 updated by: Virginia Commonwealth University

Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Other: laboratory biomarker analysis
Correlative studies
Procedure: biopsy
Optional correlative studies
Other Names:
  • biopsies
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At least 4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Up to 4 years
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.
Baseline up to 4 weeks
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.
Baseline up to 4 weeks
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.
Baseline up to 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Virginia Commonwealth University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrew Poklepovic, Massey Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MCC-13874
  • P30CA016059 (U.S. NIH Grant/Contract)
  • NCI-2011-03035 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings