AIDS-Related Kaposi SarcomaPhase 1NCT01016730
Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma
A Phase 1 study testing Bortezomib, Laboratory Biomarker Analysis and Questionnaire Administration in people with AIDS-Related Kaposi Sarcoma and HIV Infection, run by National Cancer Institute (NCI) at 9 sites in United States.
Trial summary
This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AIDS-Related Kaposi Sarcoma, HIV Infection, Recurrent Kaposi Sarcoma
- What is being tested?
- Bortezomib, Laboratory Biomarker Analysis and Questionnaire Administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 9 sitesUnited States
- Study dates
- 22 Jan 2010to 7 Jan 2015
- 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
- Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy
- Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion >= 12 mm or 3 >= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated
- Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria
- Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA
- Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
- Absolute neutrophil count (ANC) >= 1,000/mm^3; subjects may be receiving growth factor support to meet these criteria
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- Hemoglobin >= 8.0 gm/dL; subjects may be receiving growth factor support to meet these criteria
- Platelets >= 100,000/mm^3
- Total bilirubin =< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
- Serum creatinine =< institutional ULN or creatinine clearance >= 50 mL/min/1.73 m^2 for subjects with creatinine levels above institutional ULN
- Pre-existing grade 3 or 4 peripheral neuropathy
Who cannot join
- KS that is improving in the 4 weeks prior to enrollment
- Symptomatic visceral KS (oral and lymph node involvement is eligible)
- Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities of daily living is allowable
- Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
- Expected survival < 3 months with standard KS treatments (i.e., radiation, paclitaxel)
- Concurrent active opportunistic infection (OI)
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- Herpes zoster (shingles) outbreak within the last 6 months or inability to take herpes zoster prophylaxis
- Patient is =< 5 years free of another primary malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if the other primary malignancy is a localized squamous or basal cell skin cancer or cervical/anal carcinoma in situ
- Acute treatment for an infection or other serious medical illness within 14 days prior to study entry
- Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including chemotherapy, radiation therapy, biological therapy, or investigational therapy) within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment
- Prior treatment with bortezomib or other investigational proteasome inhibitors
- Previous local therapy of any KS indicator lesion within 60 days, unless the lesion has clearly progressed with enlargement since the local therapy
- Use of any investigational drug or treatment within 4 weeks prior to randomization
- Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance
- Hypersensitivity to boron
- Subjects with grade III/IV cardiac disease as defined by the New York Heart Association criteria. (e.g., congestive heart failure, myocardial infarction within 6 months of study)
- Subject has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis); subjects with known hepatitis B or C infection may be enrolled if they have either documentation of no or minimal fibrosis on liver biopsy or undetectable hepatitis virus on polymerase chain reaction (PCR)
- Systemic corticosteroid treatment, other than replacement doses
- Female subjects who are pregnant or breast-feeding
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Boston Medical Center
Boston, Massachusetts, 02118
UC San Diego Moores Cancer Center
La Jolla, California, 92093
UCLA Center for Clinical AIDS Research and Education
Los Angeles, California, 90035
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Memorial Sloan Kettering-Rockefeller Outpatient Pavilion
New York, New York, 10022
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
University of California San Diego
San Diego, California, 92103
Virginia Mason Medical Center
Seattle, Washington, 98101
About this study
Official title: Single-Arm, Dose-Finding Pilot Trial of Single-Agent Bortezomib in Patients With Relapsed/Refractory AIDS-Associated Kaposi Sarcoma With Correlative Assessments of KSHV and HIV
This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Estimate the maximum tolerated dose (MTD) of single agent bortezomib in subjects with AIDS-related Kaposi sarcoma (KS).
SECONDARY OBJECTIVES:
- Evaluate the clinical response of KS tumors to bortezomib. II. Evaluate the impact of bortezomib on human immunodeficiency virus (HIV) plasma viral loads and peripheral blood mononuclear cells (PBMC) apolipoprotein B messenger ribonucleic acid (mRNA) editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) levels.
III. Determine the impact of bortezomib on Kaposi's sarcoma-associated herpesvirus (KSHV).
IV. Assess bortezomib effects on KSHV copy number in PBMC and plasma and whether changes in viral copy number measured in PBMC and plasma are associated with clinical response of KS tumors.
- Monitor KSHV gene expression in KS biopsy specimens and PBMC pre- and post-bortezomib and assess whether changes in viral gene expression (i.e., to a lytic pattern) in tumor biopsy are associated with clinical response.
VI. Assess whether changes in viral copy number in PBMC and plasma occur in concert with or independently of changes in viral antigen expression in tumor biopsy specimens.
VII. Assess effects of bortezomib on proteins relevant to KS tumor survival and proliferation (i.e., P53, von Hippel-Lindau [VHL], p27, hypoxia-inducible factor 1 [HIF1]-alpha) as well as levels of nuclear factor-kappaB (NFkappaB) gene target mRNAs in tumor biopsies.
OUTLINE: This is a dose-escalation study.
Patients receive bortezomib intravenously (IV) on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for up to 1 year.
- Being tested
- Bortezomib, Laboratory Biomarker Analysis, Questionnaire Administration
- Medical subject headings
- AIDS-related Kaposi sarcoma, HIV Infections, Sarcoma, Kaposi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib) | Experimental | Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
MTD is defined as the highest assigned dose at which < 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.
Measured: 56 days
Secondary outcomes (5)
Change in lytic gene expression
The association between change in lytic gene expression with clinical response of KS tumors will be investigated with exact logistic regression. Hierarchical clustering will be used to explore if gene expression patterns differ according to clinical response.
Measured: Baseline to 1 year
Changes in bortezomib in KSHV copy number in PBMC and plasma
Analyzed using the Wilcoxon signed rank test. The association between change in KSHV copy number with clinical response of KS tumors will be investigated with exact logistic regression.
Measured: Baseline to 1 year
Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels
Analyzed using the Wilcoxon signed rank test.
Measured: Baseline to 1 year
Changes in viral antigen expression in biopsy specimens
Spearman's rank correlations will be calculated to examine whether the changes in KSHV viral copy number in PBMC and plasma occur in concert or independently with changes in viral antigen expression in biopsy specimens collected at baseline, day 2 and treatment discontinuation.
Measured: Baseline to 1 year
Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors
Exact binomial 95% confidence intervals will be computed. Descriptive statistics will also be presented for complete and partial response rates.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2009 (estimated)
- Study start22 Jan 2010
- Primary completion7 Jan 2015
- Study completion7 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AIDS-Related Kaposi SarcomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Erin Reid, Principal investigator, AIDS Malignancy Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01016730
- Sponsor's protocol ID
- NCI-2012-03170
- Other IDs
- NCI-2012-03170, CDR0000659554, AMC-063, AMC-063, U01CA121947, UM1CA121947
- Status last verified
- Feb 2018
- First submitted
- 18 Nov 2009
- Last updated
- 20 Feb 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Arm, Dose-Finding Pilot Trial of Single-Agent Bortezomib in Patients With Relapsed/Refractory AIDS-Associated Kaposi Sarcoma With Correlative Assessments of KSHV and HIV
- ClinicalTrials.gov ID
- NCT01016730
- Acronym / sponsor ID
- NCI-2012-03170
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 22 Jan 2010 (actual)
- Primary completion
- 7 Jan 2015 (actual)
- Study completion
- 7 Jan 2015 (actual)
- First posted
- 19 Nov 2009 (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 pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- Estimate the maximum tolerated dose (MTD) of single agent bortezomib in subjects with AIDS-related Kaposi sarcoma (KS).
SECONDARY OBJECTIVES:
- Evaluate the clinical response of KS tumors to bortezomib. II. Evaluate the impact of bortezomib on human immunodeficiency virus (HIV) plasma viral loads and peripheral blood mononuclear cells (PBMC) apolipoprotein B messenger ribonucleic acid (mRNA) editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) levels.
III. Determine the impact of bortezomib on Kaposi's sarcoma-associated herpesvirus (KSHV).
IV. Assess bortezomib effects on KSHV copy number in PBMC and plasma and whether changes in viral copy number measured in PBMC and plasma are associated with clinical response of KS tumors.
- Monitor KSHV gene expression in KS biopsy specimens and PBMC pre- and post-bortezomib and assess whether changes in viral gene expression (i.e., to a lytic pattern) in tumor biopsy are associated with clinical response.
VI. Assess whether changes in viral copy number in PBMC and plasma occur in concert with or independently of changes in viral antigen expression in tumor biopsy specimens.
VII. Assess effects of bortezomib on proteins relevant to KS tumor survival and proliferation (i.e., P53, von Hippel-Lindau [VHL], p27, hypoxia-inducible factor 1 [HIF1]-alpha) as well as levels of nuclear factor-kappaB (NFkappaB) gene target mRNAs in tumor biopsies.
OUTLINE: This is a dose-escalation study.
Patients receive bortezomib intravenously (IV) on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bortezomib) | Experimental | Drug: Bortezomib, Other: Laboratory Biomarker Analysis, Other: Questionnaire AdministrationPatients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 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 (12 listed)
- Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy
- Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion >= 12 mm or 3 >= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated
- Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria
- Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA
- Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
Key exclusion criteria (19 listed)
- KS that is improving in the 4 weeks prior to enrollment
- Symptomatic visceral KS (oral and lymph node involvement is eligible)
- Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities of daily living is allowable
- Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
- Expected survival < 3 months with standard KS treatments (i.e., radiation, paclitaxel)
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: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341Given IV | Drug | Treatment (bortezomib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (bortezomib) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (bortezomib) |
Primary outcome
MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: 56 days
MTD is defined as the highest assigned dose at which < 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.
5 secondary outcomes
Change in lytic gene expression
Time frame: Baseline to 1 year
Changes in bortezomib in KSHV copy number in PBMC and plasma
Time frame: Baseline to 1 year
Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels
Time frame: Baseline to 1 year
Changes in viral antigen expression in biopsy specimens
Time frame: Baseline to 1 year
Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors
Time frame: Up to 1 year
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 20 Feb 2018.
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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.
Erin Reid principal investigator
AIDS Malignancy Consortium
9 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, Laboratory Biomarker Analysis and Questionnaire Administration in people with AIDS-Related Kaposi Sarcoma and HIV Infection, run by National Cancer Institute (NCI) at 9 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 12 inclusion and 19 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 20 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (time frame: 56 days). 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 20 Feb 2018.