Kaposi SarcomaPhase 1/2NCT01495598
Pomalidomide for Kaposi Sarcoma in People With or Without HIV
A Phase 1/2 study testing Pomalidomide in people with Kaposi Sarcoma and Sarcoma, Kaposi, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Pomalidomide is a drug that can treat cancer through several mechanisms. It is taken by mouth (orally). Pomalidomide can help treat cancer by blocking certain factors that promote tumor growth or by stimulating the immune system to attack tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kaposi Sarcoma, Sarcoma, Kaposi
- What is being tested?
- Pomalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2012to 17 May 2022
- 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
- Age greater than or equal to 18 Years.
- Any human immunodeficiency virus (HIV) status.
- Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center, National Institutes of Health.
- At least five measurable Kaposi sarcoma (KS) lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
- Life expectancy greater than or equal to 6 months
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- For patients with HIV-associated KS:
- Must be receiving, and adherent to, a highly active antiretroviral therapy (HAART) regimen consistent with current clinical guidelines.
- Must have been receiving HAART for at least one month.
- Must have achieved an HIV viral load (VL) <10,000 copies/mL.
- The following hematological parameters:
- Hemoglobin greater than or equal to 10 g/dL
- Platelets greater than or equal to 75,000 cells/mm(3)
- Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm(3)
- The following biochemical parameters:
- Estimated or measured creatinine clearance greater than or equal to 45mL/minute
- Serum alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit of normal
- Serum aspartate aminotransferase (AST) less than or equal to 2.5 times upper limit of normal
- Bilirubin less than or equal to 1.5 times upper limit of normal unless the patient is receiving protease inhibitor therapy (e.g., indinavir, ritonavir, nelfinavir, or atazanavir) known to be associated with increased bilirubin, in which case total bilirubin less than or equal to 7.5 mg/dL with direct fraction less than or equal to 0.7 mg/dL.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 24 hours before starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, and also
- All study participants must agree to be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of the POMALYST REMS program.
- Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS program.
- Able to take aspirin 81mg daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin at a thromboprophylactic dose (such as enoxaparin 0.5mg/kg once daily).
- Willing and able to give informed consent.
- For subjects with HIV-associated entered after a tolerable dose has been determined, KS lesions must be either:
- Increasing despite HAART and HIV suppression below the limit of detection (48 copies/mL) in the two months prior to screening or
- Stable despite HAART for at least three months. Stable disease must be symptomatic (examples of symptomatic disease include disease associated with pain, edema, psychological distress and/or social withdrawal). This is to gain preliminary information about pomalidomide activity without confounding due to HAART initiation.
Who cannot join
- Symptomatic pulmonary KS.
- Symptomatic visceral KS (except for non-ulcerating disease restricted to the oral cavity).
- Specific KS therapy, including cytotoxic chemotherapy but not including HAART, within the past 4 weeks (6 weeks if the therapy was bevacizumab).
- Use of other anticancer treatments or agents within the past 4 weeks (6 weeks if the therapy was a monoclonal antibody).
- History of malignant tumors other than KS, unless:
- In complete remission for greater than or equal to 1 year from the time response was first documented or
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- Completely resected basal cell carcinoma or
- In situ squamous cell carcinoma of the cervix or anus.
- History of infection meeting any of the following criteria:
- Any infection that would be scored as grade 4 by Common Terminology Criteria for Adverse Events (CTCAE) that occurred within six weeks of study screening.
- Any infection that would be scored as grade 3 by CTCAE that occurred within two weeks of study screening.
- History of fungal and mycobacterial infections, unless at least six weeks has passed since the completion of induction antimicrobial therapy. Patients may be receiving consolidation therapy for infections of these types.
- Any abnormality that would be scored as a greater than or equal to grade 3 toxicity by CTCAE, except:
- Obesity is not considered an abnormality for the purposes of eligibility assessment unless in the opinion of the Principal Investigator or Lead Associate Investigator its clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.
- Lymphopenia
- Asymptomatic hyperuricemia, hypophosphatemia, or creatine kinase (CK) Elevations
- Direct manifestations of KS
- Direct manifestations of HIV infection, except for neurologic or cardiac manifestations
- Direct manifestations of HIV therapy, except for neurologic or cardiac manifestations.
- History of venous or arterial thromboembolism, unless:
- Line-related thrombosis without embolus occurring greater than or equal to 1 year prior to screening.
- Complications resulting from atherosclerotic coronary artery disease, peripheral vascular disease, or cerebrovascular disease (including infarction) are not considered exclusion criteria unless in the opinion of the Principal Investigator or Lead Associate Investigator their clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
- Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome.
- Pregnancy.
- Breast feeding (if lactating, must agree not to breast feed while taking pomalidomide).
- Prior therapy with pomalidomide.
- Known hypersensitivity to thalidomide, lenalidomide or pomalidomide. including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or pomalidomide.
- Any condition, including the presence of laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV
Background:
- Pomalidomide is a drug that can treat cancer through several mechanisms. It is taken by mouth (orally). Pomalidomide can help treat cancer by blocking certain factors that promote tumor growth or by stimulating the immune system to attack tumor cells. It also prevents the growth of new blood vessels that help cancer grow. Researchers want to see if pomalidomide can treat Kaposi sarcoma, a rare and potentially fatal skin cancer. Because Kaposi sarcoma may be associated with human immunodeficiency virus (HIV) infection, researchers want to test the drug in people with and without HIV infection.
Read more
Objectives:
- To see if pomalidomide is a safe and effective treatment for Kaposi sarcoma in people with or without HIV.
Eligibility:
- Individuals at least 18 years of age who have Kaposi sarcoma.
- Participants may or may not have HIV infection.
Design:
- Potential participants will be screened with a medical history and physical exam. Blood and saliva samples will be taken and a chest X-ray will be performed. A skin biopsy of a Kaposi sarcoma lesion may be performed if one has not already been done. Other imaging studies may be performed if needed.
- Participants will take pomalidomide capsules every day for 3 weeks, followed by a 1-week break. These 28 days are one cycle of treatment.
- Participants will have up six cycles of treatment, unless the lesions completely resolve sooner. If there are signs of improvement after six cycles but the lesions are not completely gone, up to another six cycles of treatment may be given.
- Treatment will be monitored with frequent blood tests and other studies including photograph and other imaging of skin lesions.
- Participants will have regular follow-up visits for 5 years after stopping treatment....
Read the detailed description
Background:
Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently involves the skin. It is seen most frequently in people with human immunodeficiency virus (HIV) or other forms of immune compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable long-term for relapsing disease are all lacking.
Objective:
The primary objective of this study is to:
Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not.
Eligibility:
- Age greater than or equal to 18 years
- Measurable, pathologically confirmed KS
- Any HIV status; HIV-associated KS subjects must be receiving and able to comply with highly active antiretroviral therapy (HAART) and have achieved an HIV viral load <10,000 copies/mL
- Hematologic and biochemical parameters within prespecified limits at baseline
- Willing to use effective birth control, as defined in the full protocol
- For subjects enrolled in the anti-tumor activity assessment phase, if KS is HIV-associated it must be increasing despite HAART and HIV suppression for greater than or equal to 2 months, or stable despite HAART for greater than or equal to 3 months
- No symptomatic pulmonary or visceral KS
- No specific KS therapy within 4 weeks (6 weeks if that therapy was bevacizumab)
- Neither pregnant nor breast feeding
Design:
This is an open label single agent phase I/II study of pomalidomide in patients with KS. In the phase I portion, up to six subjects will initially be treated with pomalidomide 5mg daily for 21 days of a 28 day cycle. Subject to toxicity evaluation, this dosage may be deescalated to 3mg daily for 21 days of a 28 day cycle in a second cohort of up to six subjects. If either dose proves tolerable, the study will proceed to the phase II portion, and additional subjects to a goal of 15 HIV positive and 10 HIV negative subjects evaluable for response will be added at the highest tolerable dose to gain preliminary information on activity.
- Conditions
- Kaposi Sarcoma, Sarcoma, Kaposi
- Being tested
- Pomalidomide
- Keywords
- Human Herpesvirus-8/HHV8, Immune Modulation, CC-4047, IMiD, Kaposi Sarcoma
- Medical subject headings
- Sarcoma, Kaposi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PomalidomideDrug
Also called POMALYST®
5 mg by mouth (p.o.) for 21 of 28 days
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Pomalidomide 5mg Daily | Experimental | Up to six subjects will initially be treated with for 21 days of a 28 day cycle Receives: Drug: Pomalidomide |
| Phase 2 Pomalidomide 5mg Daily | Experimental | 15 human immunodeficiency virus (HIV) positive and 10 HIV negative subjects evaluable for response will be treated with Pomalidomide 5mg daily for 21 days of a 28 day cycle Receives: Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide
Adverse events (AE's) that are possibly, probably, and/or definitely attributed to pomalidomide were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening.
Measured: During each cycle and 4 weeks after completing therapy, with any continuing AE's observed until resolution, approximately 124 months and 1 day.
Progression Free Survival (PFS)
PFS is defined as time from day 1 of pomalidomide therapy until progression requiring a change in therapy, estimated using the Kaplan-Meier method. Progression was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions.
Measured: time from day 1 of pomalidomide therapy until progression requiring a change in therapy, an average of 9.97 months
Maximal Plasma Concentration (Cmax) of Pomalidomide
Plasma concentrations of pomalidomide were assayed using high-performance liquid chromatography with fluorescence detection with a lower limit of quantitation of 1 ng/mL and were recorded as observed values. A non-compartmental analysis was used to calculate plasma pharmacokinetic parameters (Pharsight, Mountain View, California).
Measured: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Time to Maximum Observed Serum Concentration of Pomalidomide (Cmax)
Time to maximum observed serum concentration of Pomalidomide was reported.
Measured: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Area Under the Plasma Concentration Versus Time Curve (AUC) to the Last Timepoint (AUCLast)
Area under the plasma concentration versus time curve (AUC) was calculated using the log-linear trapezoidal method. The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measured: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Area Under the Curve Extrapolated to Infinity (AUCinf)
AUC is a measure of the serum concentration of Pomalidomide over time. It is used to characterize drug absorption. The AUC extrapolated to infinity was used, unless the percent extrapolated exceeded 25% in which case AUC to the last quantifiable time point (AUCLast) was used. The steady-state exposure on Day 15 of cycle 1 was calculated using AUCLast.
Measured: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Half-Life of Pomalidomide
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Measured: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Secondary outcomes (9)
Antitumor Effect of a Second Course of Pomalidomide
Antitumor effect of pomalidomide was assessed at the established tolerated dose after a second course of pomalidomide. Kaposi sarcoma responses were assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Complete Response (CR) required clinical resolution of all lesions and tumor-associated phenomenon with biopsy confirmation. Clinical Complete Response (cCR) is resolution of all lesions except for some residual pigmentation but who did not have a biopsy of a representative pigmented area. Partial Response (PR) required ≥ 50% decrease in the number of lesions and/or sum product of the diameters of marker lesions and/or nodularity of lesions, and no new lesions in previously uninvolved areas or criteria. Stable Disease (SD) was assessed for all participants who did not meet criteria doe CR, PR, or PD. And progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions.
Measured: After completion of 2 cycles of therapy up to 48 weeks after the start of the second course of Pomalidomide
Antitumor Effect of a First Course of Pomalidomide
Antitumor effect of pomalidomide was assessed at the established tolerated dose after a first course of pomalidomide. Kaposi sarcoma responses were assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Complete Response (CR) required clinical resolution of all lesions and tumor-associated phenomenon with biopsy confirmation. Clinical Complete Response (cCR) is resolution of all lesions except for some residual pigmentation but who did not have a biopsy of a representative pigmented area. Partial Response (PR) required ≥ 50% decrease in the number of lesions and/or sum product of the diameters of marker lesions and/or nodularity of lesions, and no new lesions in previously uninvolved areas or criteria. Stable Disease (SD) was assessed for all participants who did not meet criteria doe CR, PR, or PD. And progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions.
Measured: After completion of 2 cycles of therapy up to 48 weeks
Self-Reported Health-Related Quality of Life (HRQL) Instrument: Functional Assessment of Human Immunodeficiency Virus Infection (FAHI)
Changes in quality of life in participants receiving pomalidomide. HRQL was analyzed using a mixed-model repeated-measures analysis for FAHI and the marginal homogeneity test for Kaposi sarcoma-specific questions such as physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB), and cognitive functioning (CF). The range of possible scores for each subscale was as follows: PWB and EWB, 0 to 40; FGWB, 0 to 52; SWB, 0 to 32; CF, 0 to 12. The total FAHI score, with possible scores ranging from 0 to 176, was calculated as the sum of all five subscale values, with higher scores indicating better results. Questionnaires completed at early withdrawal visits were not included in the analyses.
Measured: Baseline, after 3 months of therapy, and after completion of therapy, up to 48 weeks
Number of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions
The number of participants responding to each question with the indicated responses is shown. Changes in quality of life in participants receiving pomalidomide. HRQL was analyzed using a mixed-model repeated-measures analysis and the marginal homogeneity test for Kaposi sarcoma-specific questions. Three supplemental questions addressing pain, swelling, and satisfaction with physical appearance was used to collect quality of life data.
Measured: Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy
Change in Cytokines From Baseline to 4 Weeks, Baseline to 8 Weeks and End of Treatment
Cytokines were evaluated using MSD 96-Well Multiarray Proinflammatory 7-plex assay (MesoScale Discovery).
Measured: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Change in Immune Cytokines Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Cluster of Differentiation 19 (CD19) Among Participants With and/or Without Human Immunodeficiency Virus (HIV)
Fluorescence activated cell sorting.
Measured: Baseline to 4 weeks, baseline to 8 weeks, and baseline to end of treatment
Change Between Timepoints Baseline to 4 Weeks, Baseline to 8 Weeks, and Baseline to End of Treatment in Kaposi Sarcoma-Associated Herpesvirus (KSHV) Viral Load
KSHV viral load in peripheral blood mononuclear cells was assessed by modifying a sandwich enzyme-linked immunosorbent assay (ELISA). Viral load testing may provide useful information on the occurrence of KSHV replication. Undetectable levels is good.
Measured: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Human Immunodeficiency Virus (HIV) Viral Load
HIV viral load in peripheral blood mononuclear cells was assessed by quantitative real-time polymerase chain reaction (PCR). The lower limit of detection for HIV viral load is <50 copies mL.
Measured: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Percentage of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions
The percentage of participants responding to each question with the indicated responses is shown. Changes in quality of life in participants receiving pomalidomide. HRQL was analyzed using a mixed-model repeated-measures analysis and the marginal homogeneity test for Kaposi sarcoma-specific questions. Three supplemental questions addressing pain, swelling, and satisfaction with physical appearance was used to collect quality of life data.
Measured: Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2011 (estimated)
- Study start10 Jan 2012
- Primary completion17 May 2022
- Study completion17 May 2022
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 (9)Papers the sponsor has linked to this study.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Robert Yarchoan, National Cancer Institute (NCI)
- Investigators
- Robert Yarchoan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01495598
- Sponsor's protocol ID
- 120047
- Other IDs
- 12-C-0047
- Status last verified
- Oct 2022
- First submitted
- 16 Dec 2011
- Last updated
- 1 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Publications
Krown SE. AIDS-associated Kaposi's sarcoma: pathogenesis, clinical course and treatment. AIDS. 1988 Apr;2(2):71-80. No abstract available.
PubMed 3132950Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. doi: 10.1126/science.7997879.
PubMed 7997879Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 2011 Jun 28;305(2):150-62. doi: 10.1016/j.canlet.2011.02.006. Epub 2011 Mar 4.
PubMed 21377267Feinberg J, Saag M, Squires K, Currier J, Ryan R, Coate B, Mrus J. Health-related quality of life in the gender, race, and clinical experience trial. AIDS Res Treat. 2011;2011:349165. doi: 10.1155/2011/349165. Epub 2011 Aug 28.
PubMed 21904672Cianfrocca M, Lee S, Von Roenn J, Tulpule A, Dezube BJ, Aboulafia DM, Ambinder RF, Lee JY, Krown SE, Sparano JA. Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer. 2010 Aug 15;116(16):3969-77. doi: 10.1002/cncr.25362.
PubMed 20564162Uldrick TS, Wang V, O'Mahony D, Aleman K, Wyvill KM, Marshall V, Steinberg SM, Pittaluga S, Maric I, Whitby D, Tosato G, Little RF, Yarchoan R. An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. Clin Infect Dis. 2010 Aug 1;51(3):350-8. doi: 10.1086/654798.
PubMed 20583924Polizzotto MN, Uldrick TS, Wyvill KM, Aleman K, Peer CJ, Bevans M, Sereti I, Maldarelli F, Whitby D, Marshall V, Goncalves PH, Khetani V, Figg WD, Steinberg SM, Zeldis JB, Yarchoan R. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol. 2016 Dec;34(34):4125-4131. doi: 10.1200/JCO.2016.69.3812. Epub 2016 Oct 31.
PubMed 27863194Ramaswami R, Polizzotto MN, Lurain K, Wyvill KM, Widell A, George J, Goncalves P, Steinberg SM, Whitby D, Uldrick TS, Yarchoan R. Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. Clin Cancer Res. 2022 Mar 1;28(5):840-850. doi: 10.1158/1078-0432.CCR-21-3364.
PubMed 34862247Lurain K, Polizzotto MN, Krug LT, Shoemaker G, Singh A, Jensen SMR, Wyvill KM, Ramaswami R, Uldrick TS, Yarchoan R, Sereti I. Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration. AIDS. 2023 Sep 1;37(11):1693-1703. doi: 10.1097/QAD.0000000000003627. Epub 2023 Jun 19.
PubMed 37352498
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV
- ClinicalTrials.gov ID
- NCT01495598
- Acronym / sponsor ID
- 120047
- Conditions
- Kaposi Sarcoma, Sarcoma, Kaposi
- Keywords
- Human Herpesvirus-8/HHV8, Immune Modulation, CC-4047, IMiD, Kaposi Sarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 10 Jan 2012 (actual)
- Primary completion
- 17 May 2022 (actual)
- Study completion
- 17 May 2022 (actual)
- First posted
- 20 Dec 2011 (estimated)
- Results
- Posted 1 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Pomalidomide is a drug that can treat cancer through several mechanisms. It is taken by mouth (orally). Pomalidomide can help treat cancer by blocking certain factors that promote tumor growth or by stimulating the immune system to attack tumor cells. It also prevents the growth of new blood vessels that help cancer grow. Researchers want to see if pomalidomide can treat Kaposi sarcoma, a rare and potentially fatal skin cancer. Because Kaposi sarcoma may be associated with human immunodeficiency virus (HIV) infection, researchers want to test the drug in people with and without HIV infection.
Objectives:
- To see if pomalidomide is a safe and effective treatment for Kaposi sarcoma in people with or without HIV.
Eligibility:
- Individuals at least 18 years of age who have Kaposi sarcoma.
- Participants may or may not have HIV infection.
Design:
- Potential participants will be screened with a medical history and physical exam. Blood and saliva samples will be taken and a chest X-ray will be performed. A skin biopsy of a Kaposi sarcoma lesion may be performed if one has not already been done. Other imaging studies may be performed if needed.
- Participants will take pomalidomide capsules every day for 3 weeks, followed by a 1-week break. These 28 days are one cycle of treatment.
- Participants will have up six cycles of treatment, unless the lesions completely resolve sooner. If there are signs of improvement after six cycles but the lesions are not completely gone, up to another six cycles of treatment may be given.
- Treatment will be monitored with frequent blood tests and other studies including photograph and other imaging of skin lesions.
- Participants will have regular follow-up visits for 5 years after stopping treatment....
Detailed description
Background:
Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently involves the skin. It is seen most frequently in people with human immunodeficiency virus (HIV) or other forms of immune compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable long-term for relapsing disease are all lacking.
Objective:
The primary objective of this study is to:
Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not.
Eligibility:
- Age greater than or equal to 18 years
- Measurable, pathologically confirmed KS
- Any HIV status; HIV-associated KS subjects must be receiving and able to comply with highly active antiretroviral therapy (HAART) and have achieved an HIV viral load <10,000 copies/mL
- Hematologic and biochemical parameters within prespecified limits at baseline
- Willing to use effective birth control, as defined in the full protocol
- For subjects enrolled in the anti-tumor activity assessment phase, if KS is HIV-associated it must be increasing despite HAART and HIV suppression for greater than or equal to 2 months, or stable despite HAART for greater than or equal to 3 months
- No symptomatic pulmonary or visceral KS
- No specific KS therapy within 4 weeks (6 weeks if that therapy was bevacizumab)
- Neither pregnant nor breast feeding
Design:
This is an open label single agent phase I/II study of pomalidomide in patients with KS. In the phase I portion, up to six subjects will initially be treated with pomalidomide 5mg daily for 21 days of a 28 day cycle. Subject to toxicity evaluation, this dosage may be deescalated to 3mg daily for 21 days of a 28 day cycle in a second cohort of up to six subjects. If either dose proves tolerable, the study will proceed to the phase II portion, and additional subjects to a goal of 15 HIV positive and 10 HIV negative subjects evaluable for response will be added at the highest tolerable dose to gain preliminary information on activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Pomalidomide 5mg Daily | Experimental | Drug: PomalidomideUp to six subjects will initially be treated with for 21 days of a 28 day cycle |
| Phase 2 Pomalidomide 5mg Daily | Experimental | Drug: Pomalidomide15 human immunodeficiency virus (HIV) positive and 10 HIV negative subjects evaluable for response will be treated with Pomalidomide 5mg daily for 21 days of a 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Age greater than or equal to 18 Years.
- Any human immunodeficiency virus (HIV) status.
- Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center, National Institutes of Health.
- At least five measurable Kaposi sarcoma (KS) lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
Key exclusion criteria (28 listed)
- Symptomatic pulmonary KS.
- Symptomatic visceral KS (except for non-ulcerating disease restricted to the oral cavity).
- Specific KS therapy, including cytotoxic chemotherapy but not including HAART, within the past 4 weeks (6 weeks if the therapy was bevacizumab).
- Use of other anticancer treatments or agents within the past 4 weeks (6 weeks if the therapy was a monoclonal antibody).
- History of malignant tumors other than KS, unless:
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 |
|---|---|---|
| PomalidomideAlso: POMALYST®5 mg by mouth (p.o.) for 21 of 28 days | Drug | Phase 1 Pomalidomide 5mg Daily, Phase 2 Pomalidomide 5mg Daily |
Primary outcome
Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide
Time frame: During each cycle and 4 weeks after completing therapy, with any continuing AE's observed until resolution, approximately 124 months and 1 day.
Adverse events (AE's) that are possibly, probably, and/or definitely attributed to pomalidomide were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening.
Progression Free Survival (PFS)
Time frame: time from day 1 of pomalidomide therapy until progression requiring a change in therapy, an average of 9.97 months
PFS is defined as time from day 1 of pomalidomide therapy until progression requiring a change in therapy, estimated using the Kaplan-Meier method. Progression was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions.
Maximal Plasma Concentration (Cmax) of Pomalidomide
Time frame: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Plasma concentrations of pomalidomide were assayed using high-performance liquid chromatography with fluorescence detection with a lower limit of quantitation of 1 ng/mL and were recorded as observed values. A non-compartmental analysis was used to calculate plasma pharmacokinetic parameters (Pharsight, Mountain View, California).
Time to Maximum Observed Serum Concentration of Pomalidomide (Cmax)
Time frame: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Time to maximum observed serum concentration of Pomalidomide was reported.
Area Under the Plasma Concentration Versus Time Curve (AUC) to the Last Timepoint (AUCLast)
Time frame: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Area under the plasma concentration versus time curve (AUC) was calculated using the log-linear trapezoidal method. The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Area Under the Curve Extrapolated to Infinity (AUCinf)
Time frame: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
AUC is a measure of the serum concentration of Pomalidomide over time. It is used to characterize drug absorption. The AUC extrapolated to infinity was used, unless the percent extrapolated exceeded 25% in which case AUC to the last quantifiable time point (AUCLast) was used. The steady-state exposure on Day 15 of cycle 1 was calculated using AUCLast.
Half-Life of Pomalidomide
Time frame: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
9 secondary outcomes
Antitumor Effect of a Second Course of Pomalidomide
Time frame: After completion of 2 cycles of therapy up to 48 weeks after the start of the second course of Pomalidomide
Antitumor Effect of a First Course of Pomalidomide
Time frame: After completion of 2 cycles of therapy up to 48 weeks
Self-Reported Health-Related Quality of Life (HRQL) Instrument: Functional Assessment of Human Immunodeficiency Virus Infection (FAHI)
Time frame: Baseline, after 3 months of therapy, and after completion of therapy, up to 48 weeks
Number of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions
Time frame: Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy
Change in Cytokines From Baseline to 4 Weeks, Baseline to 8 Weeks and End of Treatment
Time frame: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Change in Immune Cytokines Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Cluster of Differentiation 19 (CD19) Among Participants With and/or Without Human Immunodeficiency Virus (HIV)
Time frame: Baseline to 4 weeks, baseline to 8 weeks, and baseline to end of treatment
Change Between Timepoints Baseline to 4 Weeks, Baseline to 8 Weeks, and Baseline to End of Treatment in Kaposi Sarcoma-Associated Herpesvirus (KSHV) Viral Load
Time frame: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Human Immunodeficiency Virus (HIV) Viral Load
Time frame: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
Percentage of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions
Time frame: Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3132950Krown SE. AIDS-associated Kaposi's sarcoma: pathogenesis, clinical course and treatment. AIDS. 1988 Apr;2(2):71-80. No abstract available.
- Background: PubMed 7997879Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. doi: 10.1126/science.7997879.
- Background: PubMed 21377267Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 2011 Jun 28;305(2):150-62. doi: 10.1016/j.canlet.2011.02.006. Epub 2011 Mar 4.
- Background: PubMed 21904672Feinberg J, Saag M, Squires K, Currier J, Ryan R, Coate B, Mrus J. Health-related quality of life in the gender, race, and clinical experience trial. AIDS Res Treat. 2011;2011:349165. doi: 10.1155/2011/349165. Epub 2011 Aug 28.
- Background: PubMed 20564162Cianfrocca M, Lee S, Von Roenn J, Tulpule A, Dezube BJ, Aboulafia DM, Ambinder RF, Lee JY, Krown SE, Sparano JA. Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer. 2010 Aug 15;116(16):3969-77. doi: 10.1002/cncr.25362.
- Background: PubMed 20583924Uldrick TS, Wang V, O'Mahony D, Aleman K, Wyvill KM, Marshall V, Steinberg SM, Pittaluga S, Maric I, Whitby D, Tosato G, Little RF, Yarchoan R. An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. Clin Infect Dis. 2010 Aug 1;51(3):350-8. doi: 10.1086/654798.
- Results publication: PubMed 27863194Polizzotto MN, Uldrick TS, Wyvill KM, Aleman K, Peer CJ, Bevans M, Sereti I, Maldarelli F, Whitby D, Marshall V, Goncalves PH, Khetani V, Figg WD, Steinberg SM, Zeldis JB, Yarchoan R. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol. 2016 Dec;34(34):4125-4131. doi: 10.1200/JCO.2016.69.3812. Epub 2016 Oct 31.
- Results publication: PubMed 34862247Ramaswami R, Polizzotto MN, Lurain K, Wyvill KM, Widell A, George J, Goncalves P, Steinberg SM, Whitby D, Uldrick TS, Yarchoan R. Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. Clin Cancer Res. 2022 Mar 1;28(5):840-850. doi: 10.1158/1078-0432.CCR-21-3364.
- Derived from this study: PubMed 37352498Lurain K, Polizzotto MN, Krug LT, Shoemaker G, Singh A, Jensen SMR, Wyvill KM, Ramaswami R, Uldrick TS, Yarchoan R, Sereti I. Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration. AIDS. 2023 Sep 1;37(11):1693-1703. doi: 10.1097/QAD.0000000000003627. Epub 2023 Jun 19.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
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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.
Robert Yarchoan, M.D. principal investigator
National Cancer Institute (NCI)
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 Pomalidomide in people with Kaposi Sarcoma and Sarcoma, Kaposi, run by National Cancer Institute (NCI) 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 27 inclusion and 28 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 1 Nov 2022. 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 1 Nov 2022). 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?
Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide (time frame: During each cycle and 4 weeks after completing therapy, with any continuing AE's observed until resolution, approximately 124 months and 1 day.). The study lists 7 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 NCT01495598, which also lists 9 linked publications.
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 1 Nov 2022.