An Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma

June 7, 2016 updated by: Ryan Sullivan, M.D., Massachusetts General Hospital

A Phase I Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma

This research study involves the use of two investigational drugs: sorafenib and bortezomib. Sorafenib is designed to stop the growth of cells caused by changes associated with cancer. Bortezomib is designed to stop cancer cells from getting rid of waste products. This causes the cells to build up toxic levels of waste that leads to cell death. In the laboratory, the combination of sorafenib and bortezomib has been shown to fight cancer cells better than either drug alone. We are looking to determine if the combination of sorafenib and bortezomib is a safe treatment for patients with advanced melanoma. The effectiveness of this combination will also be assessed.

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

  • Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have melanoma, not everyone who participates will receive the same dose of the study drug. The dose participants will get will depend upon the number of participants who have been enrolled in the study before and how well they tolerated their doses.
  • Each treatment cycle lasts 28 days. Participants will take sorafenib orally twice a day and will receive bortezomib as an out-patient intravenous injection on Days 1, 8 and 15 of every cycle.
  • At the end of each treatment cycle, participants will be examined to determine whether their disease has worsened, improved or stayed the same, and to see if they are experiencing any side effects of treatment. The following tests will be done at these visits: physical examination, vital signs, blood tests and scans (repeated every 2 months).
  • Once the maximum tolerated dose of sorafenib and bortezomib have been determined, an additional 12 participants will be enrolled in this study. This is called the expansion cohort of this study. Participants enrolled in this cohort will be required to undergo a biopsy of the tumor lesion before they start study treatment and an additional biopsy after you start study treatment.

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.
11

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
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

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:

  • Histological or cytological confirmation of malignant melanoma that is metastatic or unresectable
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with spiral CT scan
  • Patients may have received up to 4 prior treatments for their disease including immunotherapies such as high-dose interleukin 2 and antibodies directed against the human cytotoxic T-lymphocyte antigen 4
  • 18 years of age or older
  • Life expectancy of greater than three months
  • ECOG Performance status of 0 or 1
  • Adequate organ and marrow function as outlined in the protocol
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • INT < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment wih an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events dur to agents administered more than 4 weeks earlier
  • Participants may not be receiving any other study agents
  • Known, active CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any unstable or untreated brain metastasis, or history of stroke within the past 12 months
  • Prior therapy with bortezomib, sorafenib, or other proteasome inhibitor
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib and bortezomib
  • Participants receiving any medications or substances that are inducers of CYP3A4
  • Known cardiac disease including congestive heart failure > class II NHYA, unstable angina or new onset angina, myocardial infarction within the past 6 months, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Uncontrolled intercurrent illness
  • Pregnant women
  • Individuals with a history of a different malignancy are ineligible except for the circumstances outlined in the protocol
  • HIV-positive individuals on combination antiretroviral therapy
  • Uncontrolled hypertension despite optimal medical management
  • Thrombolic or embolic events
  • Pulmonary hemorrhage/bleeding event CTCAE Grade 2 or greater within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event CTCAE Grade 3 or greater within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer or bone fracture
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Known hypersensitivity to boron or mannitol
  • Grade 2 or greater peripheral neuropathy within 14 days before enrollment

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: Dose Escalation
Drug: bortezomib
Given intravenously on days 1, 8 and 15 of each 28 day cycle
Drug: sorafenib
400mg taken orally twice a day

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
Maximally tolerated dose
Time Frame: 2 years
To determine the maximally tolerated dose of weekly bortezomib in combination with 400mg twice daily sorafenib.
2 years
Document and summarize toxicities
Time Frame: 2 years
To document and summarize the toxicities of weekly bortezomib in combination with 400mg twice daily sorafenib
2 years

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
Anti-tumor activity
Time Frame: 2 years
To document the anti-tumor activity of weekly bortezomib in combination with sorafenib by describing the six-month progression free survival, one-year progression-free survival, and objective response rate.
2 years

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.
Massachusetts General Hospital

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.
Bayer
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Millennium Pharmaceuticals, Inc.

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: Ryan J. Sullivan, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
September 1, 2010

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.
February 1, 2013

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.
June 1, 2016

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).
March 1, 2010

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.
March 1, 2010

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.
March 2, 2010

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.
June 8, 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.
June 7, 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.
January 1, 2013

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.
  • 09-443
  • X05297 (Other Identifier: Millennium Pharmaceuticals)

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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