Pomalidomide for Kaposi Sarcoma in People With or Without HIV

NCT01495598 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 12004712-C-0047
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

Kaposi Sarcoma; Sarcoma, Kaposi

Keywords

Human Herpesvirus-8/HHV8; Immune Modulation; CC-4047; IMiD; Kaposi Sarcoma

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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).

  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.

  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.

  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.

  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.

  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

  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

  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)

  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

  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

  Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment

Other Outcomes (2)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 124 months and 1 day.

• Number of Dose-limiting Toxicities

  First 8 weeks (2 cycles) of drug administration

Study Arms (2)

Phase 1 Pomalidomide 5mg Daily

EXPERIMENTAL

Up to six subjects will initially be treated with for 21 days of a 28 day cycle

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

Drug: Pomalidomide

Interventions

Pomalidomide DRUG

5 mg by mouth (p.o.) for 21 of 28 days

Also known as: POMALYST®

Phase 1 Pomalidomide 5mg Daily; Phase 2 Pomalidomide 5mg Daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Krown SE. AIDS-associated Kaposi's sarcoma: pathogenesis, clinical course and treatment. AIDS. 1988 Apr;2(2):71-80. No abstract available.

  PMID: 3132950 BACKGROUND

• Chang 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.

  PMID: 7997879 BACKGROUND

• Uldrick 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.

  PMID: 21377267 BACKGROUND

• Feinberg 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.

  PMID: 21904672 BACKGROUND

• Cianfrocca 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.

  PMID: 20564162 BACKGROUND

• Uldrick 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.

  PMID: 20583924 BACKGROUND

• Polizzotto 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.

  PMID: 27863194 RESULT

• Ramaswami 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.

  PMID: 34862247 RESULT

• Lurain 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.

  PMID: 37352498 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Results Point of Contact

• Title: Dr. Robert Yarchoan
• Organization: National Cancer Institute

robert.yarchoan@nih.gov

240-760-6075

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 20, 2011
• Study Start: January 10, 2012
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: November 1, 2022
• Results First Posted: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. All collected IPD will be available after primary analysis have been published.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)