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

Phase 1
18 Years
Open (Enrolling)

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Trial Information

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

- 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

- 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.

Inclusion Criteria:

- Histological or cytological confirmation of malignant melanoma that is metastatic or

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximally tolerated dose

Outcome Description:

To determine the maximally tolerated dose of weekly bortezomib in combination with 400mg twice daily sorafenib.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Ryan J. Sullivan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

September 2010

Completion Date:

Related Keywords:

  • Melanoma
  • bortezomib
  • sorafenib
  • advanced melanoma
  • Melanoma



Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617