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

NCT01078961 | Completed Phase 1 DMC

• 2 other identifiers: 09-443X05297
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Melanoma

Keywords

bortezomib; sorafenib; advanced melanoma

Outcome Measures

Primary Outcomes (2)

• Maximally tolerated dose

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

  2 years

• Document and summarize toxicities

  To document and summarize the toxicities of weekly bortezomib in combination with 400mg twice daily sorafenib

  2 years

Secondary Outcomes (1)

• Anti-tumor activity

  2 years

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Drug: bortezomib; Drug: sorafenib

Interventions

bortezomib DRUG

Given intravenously on days 1, 8 and 15 of each 28 day cycle

Dose Escalation

sorafenib DRUG

400mg taken orally twice a day

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator
• Bayer: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Sullivan RJ, Ibrahim N, Lawrence DP, Aldridge J, Giobbie-Hurder A, Hodi FS, Flaherty KT, Conley C, Mier JW, Atkins MB, McDermott DF. A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma. Oncologist. 2015 Jun;20(6):617-8. doi: 10.1634/theoncologist.2015-0105. Epub 2015 May 18.

  PMID: 25986244 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Bortezomib; Sorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Ryan J. Sullivan, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: March 1, 2010
• First Posted: March 2, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2016
• Last Updated: June 8, 2016

Record last verified: 2013-01

Locations

US (3)