MelanomaPhase 1NCT01078961
An Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma
A Phase 1 study testing bortezomib and sorafenib in people with Melanoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- bortezomib and sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2010to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: 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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- bortezomib, sorafenib
- Keywords
- bortezomib, sorafenib, advanced melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Given intravenously on days 1, 8 and 15 of each 28 day cycle
sorafenibDrug
400mg taken orally twice a day
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Not described Receives: Drug: bortezomib; Drug: sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximally tolerated dose
To determine the maximally tolerated dose of weekly bortezomib in combination with 400mg twice daily sorafenib.
Measured: 2 years
Document and summarize toxicities
To document and summarize the toxicities of weekly bortezomib in combination with 400mg twice daily sorafenib
Measured: 2 years
Secondary outcomes (1)
Anti-tumor activity
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2013
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bayer, Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Ryan Sullivan, M.D., Massachusetts General Hospital
- Investigators
- Ryan J. Sullivan, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01078961
- Sponsor's protocol ID
- 09-443
- Other IDs
- X05297
- Status last verified
- Jan 2013
- First submitted
- 1 Mar 2010
- Last updated
- 8 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25986244
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Expanded Cohort Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma
- ClinicalTrials.gov ID
- NCT01078961
- Acronym / sponsor ID
- 09-443
- Conditions
- Melanoma
- Keywords
- bortezomib, sorafenib, advanced melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bayer, Millennium Pharmaceuticals, Inc.
- Study start
- Sep 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 2 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: bortezomib, Drug: sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomibGiven intravenously on days 1, 8 and 15 of each 28 day cycle | Drug | Dose Escalation |
| sorafenib400mg taken orally twice a day | Drug | Dose Escalation |
Primary outcome
Maximally tolerated dose
Time frame: 2 years
To determine the maximally tolerated dose of weekly bortezomib in combination with 400mg twice daily sorafenib.
Document and summarize toxicities
Time frame: 2 years
To document and summarize the toxicities of weekly bortezomib in combination with 400mg twice daily sorafenib
1 secondary outcome
Anti-tumor activity
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2016.
- Results publication: PubMed 25986244Sullivan 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.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan J. Sullivan, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib and sorafenib in people with Melanoma, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximally tolerated dose (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01078961, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2016.