Brain and Central Nervous System TumorsPhase 1/2NCT00512798
Bortezomib and Temozolomide in Treating Patients With Advanced Refractory Solid Tumors or Melanoma
A Phase 1/2 study testing PS-341 (VELCADE), temozolomide and immunoenzyme technique in people with Brain and Central Nervous System Tumors and Melanoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors, Melanoma, Solid Tumor
- What is being tested?
- PS-341 (VELCADE), temozolomide and immunoenzyme technique
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Mar 2008
- Phase
- Phase 1/2
- 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
- Histologically proven malignancy (confirmed by Vanderbilt pathologists), advanced non-hematologic malignancy that is not curable by standard surgery, radiation therapy, or chemotherapy. Patients with melanoma, especially those with accessible tumors will be sought for this trial, but this part of the trial will not be limited to only melanoma patients
- No available effective therapy (ie; therapy known to be curative, to prolong survival, to reduce tumor-related symptoms, or to have a tangible, beneficial effect upon the patient)
- Adequate performance status for the study, Eastern Cooperative Oncology Group (ECOG) 0-1
- Adequate baseline organ system function, usually:
- Absolute neutrophil count > or equal to 1500/uL
- Hemoglobin > or equal to 9.0g/dL
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- Platelet count > or equal to 100,000/uL
- Institutional Normalized Ratio (INR) < 1.5 prior to any invasive biopsy of tumor tissue
- Creatinine < or equal to 1.5x institutional upper limit of normal (IULN) (this may be adjusted for drugs totally dependent upon or independent of renal clearance)
- Aspartate and alanine aminotransferase < or equal to 2.5x IULN, bilirubin < or equal to 1.5x IULN
- Agreement to use a barrier method of contraception, if potentially fertile
- Ability to understand and willingness to grant informed consent
- Patients with brain metastases are eligible only if the brain lesions are under control for a minimum of 4 weeks, with no progressive symptoms, and off systemic steroids. Patients with primary brain tumors are eligible if their dose of systemic steroids is stable for at least 5 days.
- Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation therapy. All treatment related toxicity must have resolved as well. Patients can not receive concomitant radiation therapy
- Patients must be 18 years of age or above and competent to sign an institutionally Institutional Review Board approved informed consent
- For the phase II trial, all patients must have advanced and incurable melanoma. Disease must be measurable. Histologic proof of disease past the primary site
- No other active malignancy including solid tumors or hematologic cancers within 24 months other than CIS, non-melanoma skin cancer, DCIS of breast, and melanoma in situ
- Melanoma patients can have up to 2 regimens of prior biologic therapies and a single regimen of systemic chemotherapy for disseminated disease.. Chemotherapy is allowed only in the chemotherapy treated patients cohort. Prior TMZ or DTIC is only allowed in those patients enrolled into the prior chemotherapy cohort
- All patients must have ECOG 0-1.
- Adequate baseline organ system function, usually:
- Absolute neutrophil count > or equal to 1500/uL
- Hemoglobin > or equal to 9.0g/dL
- Platelet count > equal to 100,000/uL
- INR < 1.5 prior to any invasive biopsy of tumor tissue
- Creatinine < or equal to 1.5x institutional upper limit of normal (IULN) (this may be adjusted for drugs totally dependent upon or independent of renal clearance)
- Aspartate and alanine aminotransferase < or equal to 2.5x IULN, bilirubin < or equal to 1.5x IULN
- Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation therapy. No prior PS-341 is allowed. All treatment related toxicity must have resolved as well. Patients can not receive concomitant radiation therapy. Prior TMZ or DTIC is only allowed in those patients enrolled into the prior chemotherapy cohort
- Patients must be 18 years of age or above and competent to sign an institutionally IRB approved informed consent.
Who cannot join
- Patients with Grade 2 or greater peripheral neuropathy
- Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make patient ineligible. No prior taxanes.
- Uncontrolled or serious infection
- New York Heart Association Class III or IV heart disease or uncontrolled angina
- Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the past 6 months
- Concurrent therapy for cancer
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- Inability to comply with protocol-specified procedures (ie, treatment, monitoring, or follow-up)
- Patients with Grade 2 or greater peripheral neuropathy.
- Uncontrolled or serious infection requiring parenteral antibiotics
- New York Heart Association Class III or IV heart disease or uncontrolled angina
- Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the past 6 months
- Concurrent therapy for cancer xiii. Inability to comply with protocol-specified procedures (ie, treatment, monitoring, or follow-up)
- Patients with brain metastases are ineligible unless the lesions have been resected or irradiated a minimum of 2 months prior to treatment, be off of steroids, and show no evidence for active disease on MRI,
- Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make patient ineligible. No prior taxanes
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: (Inhibition of NF-kB Signaling in Melanoma Therapy) A Phase I/II Clinical Trial of PS-341, a Proteasome Inhibitor, in Combination With an Extended Continuous Oral Schedule of Temozolomide in Patients With Advanced Refractory Solid Tumors With the Phase II Component Only in Patients With Melanoma
RATIONALE: Drugs used in chemotherapy, temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temozolomide together with bortezomib may kill more tumor cells.
PURPOSE: To determine the best dose of bortezomib and temozolomide and to see how well they work in treating patients with advanced refractory solid tumors or melanoma.
- Being tested
- PS-341 (VELCADE), temozolomide, immunoenzyme technique
- Keywords
- stage III melanoma, stage IV melanoma, recurrent melanoma, unspecified adult solid tumor, protocol specific, recurrent adult brain tumor, melanoma (skin)
- Medical subject headings
- Central Nervous System Neoplasms, Melanoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PS-341 (VELCADE)Drug
Also called bortezomib
Dose Levels PS-341 (day 1)
- Level -1 0.7 mg/m2
- Level 1 1.0 mg/m2
- Level 2 1.0 mg/m2
- Level 3 1.3 mg/m2
- Level 4 1.5 mg/m2
temozolomideDrug
Also called TMZ
Temozolomide (day 8)
- Level - 1 50 mg/m2
- Level 1 50 mg/m2
- Level 2 75/mg/m2
- Level 3 75 mg/m2
- Level 4 75 mg/m2
immunoenzyme techniqueOther
Also called None noted
Not noted
PS-341 (VELCADE)Drug
1.3 mg/m2 by IV on days 1, 4, 8, and 11 of every 21 days
TemozolomideDrug
75 mg/m2 by mouth, daily, during weeks 2-8 (42 days) of every 9-week course.
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | Not described Receives: Drug: PS-341 (VELCADE); Drug: temozolomide; Other: immunoenzyme technique |
| Phase II | Experimental | Not described Receives: Drug: PS-341 (VELCADE); Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal Doses of Temozolomide and Bortezomib (Phase I)
The optimal biologic dose (OBD) defined as the dose that achieves the greatest degree of inhibition of NF-κB activation in peripheral blood mononuclear cells when co-administered with Temozolomide
Measured: up to 42 days
Number of Patients With Clinical Anti-tumor Activity Phase II)
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Patients with CR + PR + SD
Measured: every 9 weeks to a maximum of 54 weeks
Secondary outcomes (3)
Patients With Inhibition in NF-kB Activation (Phase I)
Patient with a minimum of 50% reduction from baseline on day 8 or day 29 in NF-kB, measured by picograms/milliliter in peripheral mononuclear blood cells
Measured: at baseline, on day 8 and on day 29
Patients With Clinical Anti-tumor Activity (Phase I)
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Measured: every 9 weeks up to a maximum of 54 weeks
Patients With Inhibition of NF-kB (Phase II)
Patient with a minimum of 50% reduction from baseline on day 8 or day 29 in NF-kB, measured by picograms/milliliter in peripheral mononuclear blood cells
Measured: at baseline, on day 8 and on day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startJun 2003
- Primary completionJul 2006
- Study completionMar 2008
Why it stopped: This study was terminated due to lack of efficacy
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.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jeffrey A. Sosman, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Jeffrey A. Sosman, MD, Study chair, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512798
- Sponsor's protocol ID
- VICC PHI 0241
- Other IDs
- VU-VICC-PHI-0241, VU-VICC-IRB-020510
- Status last verified
- Sep 2012
- First submitted
- 6 Aug 2007
- Last updated
- 2 Oct 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (Inhibition of NF-kB Signaling in Melanoma Therapy) A Phase I/II Clinical Trial of PS-341, a Proteasome Inhibitor, in Combination With an Extended Continuous Oral Schedule of Temozolomide in Patients With Advanced Refractory Solid Tumors With the Phase II Component Only in Patients With Melanoma
- ClinicalTrials.gov ID
- NCT00512798
- Acronym / sponsor ID
- VICC PHI 0241
- Keywords
- stage III melanoma, stage IV melanoma, recurrent melanoma, unspecified adult solid tumor, protocol specific, recurrent adult brain tumor, melanoma (skin)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated due to lack of efficacy
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2003
- Primary completion
- Jul 2006 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 8 Aug 2007 (estimated)
- Results
- Posted 3 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temozolomide together with bortezomib may kill more tumor cells.
PURPOSE: To determine the best dose of bortezomib and temozolomide and to see how well they work in treating patients with advanced refractory solid tumors or melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: PS-341 (VELCADE), Drug: temozolomide, Other: immunoenzyme technique |
| Phase II | Experimental | Drug: PS-341 (VELCADE), Drug: Temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Histologically proven malignancy (confirmed by Vanderbilt pathologists), advanced non-hematologic malignancy that is not curable by standard surgery, radiation therapy, or chemotherapy. Patients with melanoma, especially those with accessible tumors will be sought for this trial, but this part of the trial will not be limited to only melanoma patients
- No available effective therapy (ie; therapy known to be curative, to prolong survival, to reduce tumor-related symptoms, or to have a tangible, beneficial effect upon the patient)
- Adequate performance status for the study, Eastern Cooperative Oncology Group (ECOG) 0-1
- Adequate baseline organ system function, usually:
- Agreement to use a barrier method of contraception, if potentially fertile
Key exclusion criteria (14 listed)
- Patients with Grade 2 or greater peripheral neuropathy
- Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make patient ineligible. No prior taxanes.
- Uncontrolled or serious infection
- New York Heart Association Class III or IV heart disease or uncontrolled angina
- Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the past 6 months
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 |
|---|---|---|
| PS-341 (VELCADE)Also: bortezomibDose Levels PS-341 (day 1) * Level -1 0.7 mg/m2 * Level 1 1.0 mg/m2 * Level 2 1.0 mg/m2 * Level 3 1.3 mg/m2 * Level 4 1.5 mg/m2 | Drug | Phase I |
| temozolomideAlso: TMZTemozolomide (day 8) * Level - 1 50 mg/m2 * Level 1 50 mg/m2 * Level 2 75/mg/m2 * Level 3 75 mg/m2 * Level 4 75 mg/m2 | Drug | Phase I |
| immunoenzyme techniqueAlso: None notedNot noted | Other | Phase I |
| PS-341 (VELCADE)1.3 mg/m2 by IV on days 1, 4, 8, and 11 of every 21 days | Drug | Phase II |
| Temozolomide75 mg/m2 by mouth, daily, during weeks 2-8 (42 days) of every 9-week course. | Drug | Phase II |
Primary outcome
Optimal Doses of Temozolomide and Bortezomib (Phase I)
Time frame: up to 42 days
The optimal biologic dose (OBD) defined as the dose that achieves the greatest degree of inhibition of NF-κB activation in peripheral blood mononuclear cells when co-administered with Temozolomide
Number of Patients With Clinical Anti-tumor Activity Phase II)
Time frame: every 9 weeks to a maximum of 54 weeks
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Patients with CR + PR + SD
3 secondary outcomes
Patients With Inhibition in NF-kB Activation (Phase I)
Time frame: at baseline, on day 8 and on day 29
Patients With Clinical Anti-tumor Activity (Phase I)
Time frame: every 9 weeks up to a maximum of 54 weeks
Patients With Inhibition of NF-kB (Phase II)
Time frame: at baseline, on day 8 and on day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeffrey A. Sosman, MD study chair
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PS-341 (VELCADE), temozolomide and immunoenzyme technique in people with Brain and Central Nervous System Tumors and Melanoma, run by Vanderbilt-Ingram 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 28 inclusion and 14 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: stopped early, as of the sponsor's last update on 2 Oct 2012. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Aug 2012). 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?
Optimal Doses of Temozolomide and Bortezomib (Phase I) (time frame: up to 42 days). 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?
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 2 Oct 2012.