Sorafenib in Treating Patients With Advanced Solid Tumors

February 21, 2014 updated by: National Cancer Institute (NCI)

A Dose Escalation Study of Sorafenib (BAY 43-9006, NSC 724772) in Nomotensive Patients With Advanced Malignancies

This randomized phase I trial is studying the side effects, such as high blood pressure, and best dose of sorafenib in treating patients with advanced solid tumors. 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.

Study Overview

Status

Status

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

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. Determine whether increasing the dose of sorafenib tosylate increases the plasma steady-state concentration in patients with advanced solid tumors.

II. Determine whether increasing the dose of this drug affects blood pressure in these patients.

SECONDARY OBJECTIVES:

I. Determine whether the variability in blood pressure elevation is due to pharmacokinetic or pharmacodynamic variability.

II. Compare the toxicity and differences in pharmacokinetics of delivering a higher dose of this drug per day (using two different schedules) vs delivering the currently recommended dose of this drug.

III. Investigate mechanisms of sorafenib tosylate-induced hypophosphatemia with serial measurements of phosphate metabolism (no longer assessed as of 4/29/2009) in these patients, detailed baseline measurements in all patients, and detailed evaluations of patients developing grade 3 or greater hypophosphatemia.

IV. Detect subclinical effects of this drug on measures of thyroid function. V. Identify biomarkers predicting the categorization of patient response.

OUTLINE: This is a randomized, dose-escalation study.

Patients receive oral sorafenib tosylate twice daily on days 1-7 and once on day 8. Patients not experiencing at least one grade 2 or higher toxicity during the initial sorafenib treatment are randomized to 1 of 3 dose-escalated treatment arms.

ARM I: Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.

ARM II: Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.

ARM III: (closed to accrual as of 4/29/2009) Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36.

In all arms, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo ambulatory blood pressure monitoring at baseline, on days 7, 14, and 21, and at 6 and 12 months. Blood samples are collected periodically throughout study and evaluated for pharmacokinetic studies, thyroid function, serum markers, and phosphate metabolism*. CT perfusion imaging is performed at baseline, week 6, week 12, and then every 8-12 weeks thereafter.

NOTE: * Phosphate metabolism no longer assessed as of 4/29/2009.

After completion of study treatment, patients are followed every 4 weeks for 1 year and then every 3 months thereafter.

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.
110

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
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago

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

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed malignant solid tumor

    • Refractory disease for which curative or palliative measures have failed or for which there is no known superior treatment
    • No colorectal cancer or melanoma
  • Measurable OR nonmeasurable disease

  • Normotensive (blood pressure [BP] ≤ 140/90 mm Hg) meeting 1 of the following criteria:

    • No more than 2 attempted measurement sessions for which the documented mean systolic BP is ≤ 140 mm Hg and the diastolic BP is ≤ 90 mm Hg
    • At least 30 attempted measurement sessions for which the documented mean systolic BP is ≤ 135 mm HG and the diastolic BP is ≤ 85 mm Hg

  • Brain metastases allowed provided the following criteria are met:

    • Stable neurologic status for ≥ 2 weeks after completion of definitive local therapy (surgery or radiotherapy)
    • No neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • ECOG performance status 0-1
  • Life expectancy > 12 weeks
  • Age ≥ 14 years OR weight ≥ 45 kilograms (pediatric patients)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (5 times ULN if there is liver involvement)
  • Creatinine ≤ 1.5 times ULN
  • No New York Heart Association class II-IV congestive heart failure
  • No unstable angina (anginal symptoms at rest) or new-onset angina (began within the past 3 months)
  • No myocardial infarction within the past 6 months
  • No ventricular arrhythmias requiring anti-arrhythmic therapy
  • No thrombotic or embolic events, such as symptomatic pulmonary embolus or any cerebrovascular accident (including transient ischemic attacks) within the past 6 months
  • No pulmonary hemorrhage/bleeding event > grade 2 within the past 4 weeks
  • No other hemorrhage/bleeding event > grade 3 within the past 4 weeks
  • No evidence or history of bleeding diathesis or coagulopathy
  • No serious nonhealing wound, ulcer, or bone fracture
  • No ongoing or active infection > grade 2
  • No psychiatric illness or social situation that would limit compliance with study requirements
  • No allergy to sorafenib tosylate or excipients
  • No unstable condition that would jeopardize the safety of the patient and/or her/his compliance with the study
  • No significant traumatic injury within the past 4 weeks
  • No condition that would impair the patient's ability to swallow whole pills or capacity to absorb oral medications
  • No seizure disorder requiring steroids or anticonvulsant therapy
  • No other concurrent illness
  • Recovered from prior therapy

  • Prior vascular endothelial growth factor (VEGF) pathway inhibitor (e.g., bevacizumab, sunitinib malate, axitinib) allowed provided the following criteria are met:

    • The patient's best response as measured by RECIST criteria was not progressive disease
    • If the most recent agent was a small molecule reversible inhibitor (e.g., sunitinib malate, cediranib, or axitinib), the patient must not have taken a dose of the agent within 2 weeks of the baseline blood pressure session and 3 weeks of starting sorafenib tosylate
    • If the most recent agent was bevacizumab or VEGF trap the patient must not have received the most recent dose within 5 weeks of the baseline blood pressure session and 6 weeks of starting sorafenib tosylate AND no grade 3 bleeding, cardiovascular, skin, or thyroid toxicities on one of these previous therapies
  • More than 2 weeks since prior and no concurrent radiotherapy
  • At least 3 weeks since prior and no concurrent chronic epoetin alfa (or congeners)
  • More than 3 weeks since prior immunotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior major surgery or open biopsy
  • At least 3 weeks since prior uncharacterized herbal agents or nutritional supplements
  • More than 12 weeks since prior radioimmunotherapy
  • No prior sorafenib tosylate

  • No prior organ allograft or allogeneic bone marrow or peripheral blood stem cell transplantation

    • Patients with a history of autologous transplant and normal bone marrow function are eligible
  • No prior cyclosporine, Hypericum perforatum (St. John's wort), or rifampin
  • No other concurrent investigational agents
  • No other concurrent antineoplastic therapy, including chemotherapy, except androgen-ablating agents (for patients with prior prostate cancer)
  • No concurrent hematopoietic growth factors
  • No concurrent combination antiretroviral therapy for HIV-positive or chronic hepatitis B-positive patients

  • No concurrent hormonal therapy except steroids for adrenal insufficiency or hormones for nondisease-related conditions (e.g., insulin for diabetes)

    • Steroids for autoimmune cytopenia allowed provided dose has been stable for 3 weeks
  • No anticipated need for other antineoplastic therapy within the next 4 weeks

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: Randomized
  • 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: Arm I (higher-dose enzyme inhibitor therapy)
Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
Other: pharmacological study
Other Names:
  • pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Procedure: assessment of therapy complications
Ancillary studies
Active Comparator: Arm II (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
Other: pharmacological study
Other Names:
  • pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Procedure: assessment of therapy complications
Ancillary studies
Active Comparator: Arm III (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009)
Other: pharmacological study
Other Names:
  • pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Procedure: assessment of therapy complications
Ancillary studies

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
Changes in BP
Time Frame: From baseline to day 21
BP will first be calculated for each subject as BP after 1 week of treatment minus BP before that treatment dose. Then, for each randomized group separately, the BP changes in the two study phases will be compared using paired t-tests.
From baseline to day 21

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
Association between steady state trough levels of sorafenib and BP
Time Frame: Days 8 and 22
Spearman correlation coefficients (since the distribution of sorafenib plasma trough levels is not normal and the relationship may be non-linear) will be calculated and scatter plots will be produced separately for each phase of the study. The association between differences in trough levels at the two different doses and changes in BP due to dose escalation will be tested in a similar manner. comparisons of BP changes and drug plasma levels between the three randomized treatment arms will be analyzed by analysis of variance (ANOVA) followed by Tukey's allowance for multiple comparisons.
Days 8 and 22
Toxicity rates in the two high dose groups
Time Frame: Every 2 weeks, assessed up to 1 year
Toxicity rates will be summarized by type, grade, and attribution and compared using chi-squared tests or Fisher exact tests, as appropriate.
Every 2 weeks, assessed up to 1 year
Effect of sorafenib dose/exposure on thyroid function
Time Frame: From baseline up to 50 days
Analysis of variance for repeated measures with one between groups factor (sorafenib dose) and one within subjects factor (time) will be used on serum parathyroid hormone (PTH).
From baseline up to 50 days

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.
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: Michael Maitland, University of Chicago

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.
January 1, 2007

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.
September 1, 2011

Study Completion

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.
December 7, 2022

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).
February 15, 2007

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.
February 15, 2007

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.
February 19, 2007

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 24, 2014

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 21, 2014

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.
October 1, 2011

More Information

Terms related to this study

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.
  • NCI-2009-00221 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA014599 (U.S. NIH Grant/Contract)
  • UCCRC-15002A
  • CDR0000528261
  • 15002A (Other Identifier: University of Chicago)
  • 7768 (Other Identifier: CTEP)
  • U01CA069852 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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