MelanomaPhase 1NCT01462773
Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma
A Phase 1 study testing Bortezomib and Interferon Alfa-2b in people with Melanoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety, tolerability and dose limiting toxicities (DLTs) of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma. 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 Interferon Alfa-2b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Apr 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- must have histological or cytological diagnosis of cutaneous melanoma and clinical evidence of metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease. Patients who have had resected metastases will also be eligible provided they have measurable disease.
- have measurable disease. Measurable disease is defined as the presence of at least one measurable lesion.
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
- Female subjects must be either surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subjects must agree to use an acceptable method for contraception for the duration of the study.
- Patients must have normal organ and marrow function.
- Prior Therapy: Patients with an ECOG performance status of ≤ 2 will be eligible for this protocol regardless of the number of prior treatments provided they have recovered from the reversible effects of prior therapy. Patients are permitted to have received therapy with adjuvant IFN-α2b, if it was completed > 6 months prior to enrollment in the current study.
- Patients with brain metastases are eligible for entry into the study, but must have received definitive therapy consisting of external beam radiation therapy, gamma knife therapy or surgical resection and be clinically stable. Four weeks after the definitive therapy is completed, repeat MRI or CT scans must demonstrate stabilization of disease, and there must be no requirement for Decadron. If the patient does not have brain metastases, then only one brain CT or MRI is required prior to enrollment on study.
Who cannot join
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- Patient has a platelet count of < 100 × 109/L within 14 days before enrollment.
- Patient has an absolute neutrophil count of < 1.0 x 109/L within 14 days before enrollment.
- Patient has a calculated or measured creatinine clearance of < 30 mL/minute within 14 days before enrollment.
- Patient has history of significant brain metastases or other clinically significant central nervous system disease.
- Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
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- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Patients with evidence of proteinuria on urinalysis.
- Female subject is pregnant or breast-feeding.
- Received other investigational drugs with 14 days before enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- History of serious psychiatric illness that might be exacerbated by IFN-α-2b.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma.
The purpose of this study is to determine the safety, tolerability and dose limiting toxicities (DLTs) of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.
Read the detailed description
The primary objective of this study is to:
- Determine the safety, tolerability and DLTs of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.
The secondary objectives of this study are to:
- Document any objective anti-tumor responses that may occur in response to this treatment regimen.
- Document the time to tumor progression in patients receiving this treatment regimen.
- Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies obtained pre-study and during week 4 of Cycle 1 (Day 26).
- Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic infiltrates within tumor biopsies obtained pre- and post-study.
- Measure plasma levels of bFGF and VEGF over the course of the study.
- Monitor the effects of proteasome inhibition on the biological activity of IFN-α within immune cells by measuring Jak-STAT signal transduction in patient PBMCs.
- Conditions
- Melanoma
- Being tested
- Bortezomib, Interferon Alfa-2b
- Keywords
- malignant, 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
Also called VELCADE®
VELCADE (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2 IV based on patient cohort). After three patients have received 5 weeks of therapy (1 cycle) at the initial dose of VELCADE (1.0 mg/m2, Cohort 1) with no dose limiting toxicity, the dose will be raised to 1.3 mg/m2 for the next cohort of three patients. If this dose level is well-tolerated in three consecutive patients, the dose of VELCADE will be raised to 1.6 mg/m2.
Interferon Alfa-2bDrug
Also called IFN-α-2b
I = IFN-α-2b (INTRON A): 5 million units (MU)/m2 SC. INTRON A (5MU/m2) will be administered subcutaneously on Days 1, 3 and 5 of Week 0. During Cycle I, INTRON A will be administered on Days 1, 3 and 5 of Weeks 1-3 of and on Days 1 and 3 of Week 4 to allow for surgical biopsy on Day 5. During Cycles II-V, IFN-α will be administered on Days 1, 3 and 5 of Weeks 1-4. To assess the toxicity profile of IFN-α-2b alone, no VELCADE will be administered during Week 0.
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor, interferon therapy) | Experimental | Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22 and recombinant interferon alfa-2b SC on days 1, 3, and 5 (days 1 and 3 only in week 4 course 1) of weeks 1-4. Treatment repeats every 5 weeks for 5 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Drug: Interferon Alfa-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma.
A standard method for the design of this study. Initially, three patients will be treated at a starting dose of VELCADE (1.0 mg/m2). If one of the three patients demonstrates a DLT, then an additional 3 patients will be treated at that dose level. If only one of the six show DLT, then the next cohort of three patients will be entered at the next dose level (1.3 mg/m2). If two or more of the six demonstrate DLT, no further patients will be treated at that dose level. The highest dose level at which less than 2 patients experienced DLT will be expanded to six patients.
Measured: up to 25 weeks or until disease progression
Secondary outcomes (1)
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen.
- Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies obtained pre-study and during week 4 of Cycle 1 (Day 26).
- Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic infiltrates within tumor biopsies obtained pre- and post-study.
- Measure plasma levels of bFGF and VEGF over the course of the study.
- Monitor the effects of proteasome inhibition on the biological activity of IFN-α within immune cells by measuring Jak-STAT signal transduction in patient PBMCs.
Measured: up to 25 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2011 (estimated)
- Study startJan 2006
- Primary completionOct 2010
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 Ohio State University Comprehensive Cancer CenterThe 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
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Carson, Ohio State University Comprehensive Cancer Center
- Investigators
- William Carson, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01462773
- Sponsor's protocol ID
- OSU-04105
- Other IDs
- NCI-2011-03174
- Status last verified
- Dec 2014
- First submitted
- 19 Oct 2011
- Last updated
- 13 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Markowitz J, Luedke EA, Grignol VP, Hade EM, Paul BK, Mundy-Bosse BL, Brooks TR, Dao TV, Kondalasula SV, Lesinski GB, Olencki T, Kendra KL, Carson WE 3rd. A phase I trial of bortezomib and interferon-alpha-2b in metastatic melanoma. J Immunother. 2014 Jan;37(1):55-62. doi: 10.1097/CJI.0000000000000009.
PubMed 24316557
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma.
- ClinicalTrials.gov ID
- NCT01462773
- Acronym / sponsor ID
- OSU-04105
- Conditions
- Melanoma
- Keywords
- malignant, melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Oct 2010 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 31 Oct 2011 (estimated)
- Results
- Posted 30 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety, tolerability and dose limiting toxicities (DLTs) of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.
Detailed description
The primary objective of this study is to:
- Determine the safety, tolerability and DLTs of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.
The secondary objectives of this study are to:
- Document any objective anti-tumor responses that may occur in response to this treatment regimen.
- Document the time to tumor progression in patients receiving this treatment regimen.
- Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies obtained pre-study and during week 4 of Cycle 1 (Day 26).
- Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic infiltrates within tumor biopsies obtained pre- and post-study.
- Measure plasma levels of bFGF and VEGF over the course of the study.
- Monitor the effects of proteasome inhibition on the biological activity of IFN-α within immune cells by measuring Jak-STAT signal transduction in patient PBMCs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor, interferon therapy) | Experimental | Drug: Bortezomib, Drug: Interferon Alfa-2bPatients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22 and recombinant interferon alfa-2b SC on days 1, 3, and 5 (days 1 and 3 only in week 4 course 1) of weeks 1-4. Treatment repeats every 5 weeks for 5 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- must have histological or cytological diagnosis of cutaneous melanoma and clinical evidence of metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease. Patients who have had resected metastases will also be eligible provided they have measurable disease.
- have measurable disease. Measurable disease is defined as the presence of at least one measurable lesion.
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
- Female subjects must be either surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subjects must agree to use an acceptable method for contraception for the duration of the study.
- Patients must have normal organ and marrow function.
Key exclusion criteria (12 listed)
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
- Patient has a calculated or measured creatinine clearance of < 30 mL/minute within 14 days before enrollment.
- Patient has history of significant brain metastases or other clinically significant central nervous system disease.
- Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
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 |
|---|---|---|
| BortezomibAlso: VELCADE®VELCADE (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2 IV based on patient cohort). After three patients have received 5 weeks of therapy (1 cycle) at the initial dose of VELCADE (1.0 mg/m2, Cohort 1) with no dose limiting toxicity, the dose will be raised to 1.3 mg/m2 for the next cohort of three patients. If this dose level is well-tolerated in three consecutive patients, the dose of VELCADE will be raised to 1.6 mg/m2. | Drug | Treatment (enzyme inhibitor, interferon therapy) |
| Interferon Alfa-2bAlso: IFN-α-2bI = IFN-α-2b (INTRON A): 5 million units (MU)/m2 SC. INTRON A (5MU/m2) will be administered subcutaneously on Days 1, 3 and 5 of Week 0. During Cycle I, INTRON A will be administered on Days 1, 3 and 5 of Weeks 1-3 of and on Days 1 and 3 of Week 4 to allow for surgical biopsy on Day 5. During Cycles II-V, IFN-α will be administered on Days 1, 3 and 5 of Weeks 1-4. To assess the toxicity profile of IFN-α-2b alone, no VELCADE will be administered during Week 0. | Drug | Treatment (enzyme inhibitor, interferon therapy) |
Primary outcome
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma.
Time frame: up to 25 weeks or until disease progression
A standard method for the design of this study. Initially, three patients will be treated at a starting dose of VELCADE (1.0 mg/m2). If one of the three patients demonstrates a DLT, then an additional 3 patients will be treated at that dose level. If only one of the six show DLT, then the next cohort of three patients will be entered at the next dose level (1.3 mg/m2). If two or more of the six demonstrate DLT, no further patients will be treated at that dose level. The highest dose level at which less than 2 patients experienced DLT will be expanded to six patients.
1 secondary outcome
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen.
Time frame: up to 25 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24316557Markowitz J, Luedke EA, Grignol VP, Hade EM, Paul BK, Mundy-Bosse BL, Brooks TR, Dao TV, Kondalasula SV, Lesinski GB, Olencki T, Kendra KL, Carson WE 3rd. A phase I trial of bortezomib and interferon-alpha-2b in metastatic melanoma. J Immunother. 2014 Jan;37(1):55-62. doi: 10.1097/CJI.0000000000000009.
- JameslineLink provided by the sponsor.
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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.
William Carson, MD principal investigator
Ohio State University
1 site 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 Interferon Alfa-2b in people with Melanoma, run by Ohio State University Comprehensive Cancer Center at 1 site 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 7 inclusion and 12 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 13 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 30 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma. (time frame: up to 25 weeks or until disease progression). 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 NCT01462773, 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 13 Jan 2015.