Clinical Trials /

Pomalidomide Treatment in Patients With Kaposi Sarcoma

NCT04577755

Description:

This phase II trial studies the effect of pomalidomide in treating patients with Kaposi sarcoma. Pomalidomide is a cancer fighting drug that stops the growth of blood vessels, stimulates the immune system, and may kill cancer cells.

Related Conditions:
  • Skin Kaposi Sarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pomalidomide Treatment in Patients With Kaposi Sarcoma
  • Official Title: Multicenter Phase II Study of Pomalidomide Monotherapy in Kaposi Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2020-07565
  • SECONDARY ID: NCI-2020-07565
  • SECONDARY ID: AMC-108
  • SECONDARY ID: AMC-108
  • SECONDARY ID: UM1CA121947
  • NCT ID: NCT04577755

Conditions

  • Skin Kaposi Sarcoma

Interventions

DrugSynonymsArms
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystTreatment (pomalidomide)

Purpose

This phase II trial studies the effect of pomalidomide in treating patients with Kaposi sarcoma. Pomalidomide is a cancer fighting drug that stops the growth of blood vessels, stimulates the immune system, and may kill cancer cells.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess the proportion of participants with Kaposi sarcoma (KS) (with or without human
      immunodeficiency virus [HIV], regardless of previous treatment status) treated with
      pomalidomide who respond to treatment with a durable response (i.e., response duration of at
      least one year).

      SECONDARY OBJECTIVES:

      I. To determine progression free survival (PFS) in participants with KS. II. To estimate the
      overall response rate (ORR) in subgroups of KS in regard to HIV and previous treatment
      status.

      III. To assess the safety of pomalidomide therapy.

      EXPLORATORY OBJECTIVES:

      I. To assess the effect of pomalidomide treatment on the tumor microenvironment and explore
      the relationship with clinical response.

      II. To describe the effects of pomalidomide on CD4 lymphocyte counts and HIV viral load in
      HIV positive (+) participants.

      III. To assess the effect of pomalidomide treatment on serum biomarkers and explore the
      relationship with clinical response.

      IV. To assess Kaposi's sarcoma-associated herpesvirus (KSHV) viral copy number in plasma and
      explore whether changes correlate with clinical outcome.

      OUTLINE:

      Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats
      every 28 days for up to 12 cycles in the absence of disease progression or unacceptable
      toxicity. After 12 cycles, patients with complete response, partial response, or stable
      disease may continue pomalidomide for an additional 12 cycles in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for up to 5
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pomalidomide)ExperimentalPatients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 12 cycles, patients with complete response, partial response, or stable disease may continue pomalidomide for an additional 12 cycles in the absence of disease progression or unacceptable toxicity.
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Participant is able to understand and willing to sign a written informed consent
             document

          -  Participants must have histologically or cytologically confirmed cutaneous Kaposi
             sarcoma. Participants must have measurable disease with a minimum of five
             bi-dimensionally measurable KS cutaneous marker lesions. If fewer than five
             bi-dimensionally measurable marker lesions are available, the total surface area of
             the marker lesion(s) must be >= 700 mm^2

          -  Participants must have documentation of HIV status

               -  If HIV negative, documentation of a negative HIV rapid test within 21 days before
                  enrollment

               -  If HIV positive, documentation of HIV-1 infection by means of any one of the
                  following:

                    -  Documentation of HIV diagnosis in the medical record by a licensed health
                       care provider

                    -  Documentation of receipt of antiretroviral therapy (ART) (at least two
                       different medications that do not constitute a prescription for pre-exposure
                       prophylaxis [PrEP]) by a licensed health care provider. Documentation may be
                       a record of an ART prescription in the participant's medical record, a
                       written prescription in the name of the participant for ART, or pill bottles
                       for ART with a label showing the participant's name

                    -  Any licensed HIV screening antibody and/or HIV antibody/antigen combination
                       assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot
                       confirmation or HIV rapid multispot antibody differentiation assay

               -  Note: The term "licensed" refers to a kit that has been certified or licensed by
                  an oversight body within the participating country and validated internally
                  (e.g., United States [U.S.] Food and Drug Administration [FDA])

               -  WHO (World Health Organization) and CDC (Centers for Disease Control and
                  Prevention) guidelines mandate that confirmation of the initial test result must
                  use a test that is different from the one used for the initial assessment. A
                  reactive initial rapid test should be confirmed by either another type of rapid
                  assay or an enzyme (E)/carbon immunoassay (CIA) that is based on a different
                  antigen preparation and/or different test principle (e.g., indirect versus
                  competitive), or a Western blot or a plasma HIV-1 ribonucleic acid (RNA) viral
                  load

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1

          -  Life expectancy of greater than 6 months

          -  Hemoglobin >= 8 g/dL (within 7 days before enrollment)

          -  Absolute neutrophil count (ANC): >= 1,000/mm^3 (within 7 days before enrollment)

          -  Platelets: >= 75,000/mm^3 (within 7 days before enrollment)

          -  Bilirubin =< 1.5: x upper limit of normal (ULN) unless the patient is receiving an ART
             drug known to be associated with increased bilirubin, in which case the direct
             fraction should be =< 2 x ULN (within 7 days before enrollment)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional ULN (within 7 days before enrollment)

          -  Serum creatinine =< 2.0 mg/dL/176.8 umol/L; or estimated creatinine clearance >= 15
             mL/minute (1.00 mL/s) (as calculated per the Cockcroft-Gault equation (within 7 days
             before enrollment)

          -  Females of childbearing potential (FCBP, defined as a sexually mature woman who: 1)
             has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
             naturally postmenopausal for at least 24 consecutive months, i.e., has had menses at
             any time in the preceding 24 consecutive months) must have a negative serum or urine
             pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and
             again within 24 hours of 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 patients must be counseled at a
             minimum of every 28 days about pregnancy precautions and risks of fetal exposure

          -  HIV positive participants must be taking stable ART for >= 12 weeks, and have an
             undetectable HIV viral load within 28 days before enrollment. Minor fluctuations up to
             200 copies/mL are acceptable

          -  HIV positive participants must not show recent improvement on ART that may confound
             response evaluation, within the following parameters:

               -  If on ART 12 to 24 weeks, participants must show evidence of KS progression
                  requiring further systemic treatment

               -  If on ART for > 24 weeks, must show no evidence of regression in last 8 weeks

          -  Participants must agree to participate in and comply with the mandatory POMALYST Risk
             Evaluation and Mitigation Strategy (REMS) program

          -  Participants must be able to take aspirin 81 mg daily as prophylactic anticoagulation
             (patients intolerant to acetylsalicylic acid (ASA), may use warfarin or low molecular
             weight heparin)

        Exclusion Criteria:

          -  Participant who is receiving any other investigational agents

          -  Participant has symptomatic visceral KS involving the lungs or gastrointestinal (GI)
             tract

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pomalidomide

          -  Use of agents containing zidovudine (including Combivir and Trizivir) are prohibited.
             Changes to ART therapy during the study may be made if medically necessary (toxicity,
             failure of regimen, etc.). Use of medications or substances that are strong inhibitors
             of CYP1A2, which include amiodarone, cimetidine, fluoroquinolones (e.g.,
             ciprofloxacin, enoxacin), fluvoxamine, and ticlopidine is prohibited.
             Co-administration of efavirenz, an inhibitor of CYP1A2, with strong inhibitors of
             CYP3A4 and P-glycoprotein (P-gp) is prohibited. Use of erythropoietin is prohibited.
             Co-administration of corticosteroids greater than doses required for treatment of
             adrenal insufficiency is prohibited. Because the lists of these agents are constantly
             changing, it is important to regularly consult frequently-updated list; medical
             reference texts such as the Physicians' Desk Reference may also provide this
             information. As part of the informed consent/enrollment procedures, the participant
             will be counseled on the risk of interactions with other agents, and what to do if new
             medications need to be prescribed or if the participant is considering a new
             over-the-counter medicine or herbal product

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection for which the participants have not completed at least 14 days of therapy
             prior to study enrollment and/or is not clinically stable

          -  Participant has symptomatic congestive heart failure; unstable angina pectoris;
             cardiac arrhythmia; or psychiatric illness/social situations that, in the opinion of
             the investigator, would limit compliance with study requirements

          -  Pregnant women are excluded from this study because pomalidomide is a thalidomide
             analogue with the potential for teratogenic or abortifacient effects. Because there is
             an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with pomalidomide, breastfeeding should be discontinued if the
             mother is treated with pomalidomide

          -  Participants who have had chemotherapy, radiotherapy, or therapies to target KS
             lesions within 4 weeks (6 weeks for nitrosoureas or mitomycin C) with the exception of
             ART, before enrollment

          -  Participants with high clinical suspicion of concurrent Castleman disease or IL-6
             related inflammatory disease

               -  For a reference of signs and symptoms consistent with IL-6 related inflammatory
                  disease or KSHV inflammatory cytokine syndrome (KICS) can refer to publication
                  from Polizzotto Minnesota (MN), et al. Clinical Features and Outcomes of Patients
                  with Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation:
                  Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS).
                  Clinical Infectious Diseases, 2016. 62(6):730-8

          -  Participants with a history of malignant tumors other than KS, unless:

               -  In complete remission for >= 1 year, or

               -  Completely resected basal cell or squamous skin carcinoma, or

               -  In situ squamous cell carcinoma (SCC) of the cervix or anus

          -  Participants with grade >= 3 peripheral neuropathy

          -  Participants with a history of venous or arterial thromboembolism, unless line-rated
             thrombosis without embolus occurring >= 1 year prior to study entry

          -  Participants with a known procoagulant disorder including prothrombin gene mutation
             20210, antithrombin III deficiency, protein C deficiency, protein S deficiency, or
             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

          -  Participants with any prior use of pomalidomide, lenalidomide or thalidomide

          -  Participants with any condition, including the presence of laboratory abnormalities,
             which in the opinion of the responsible investigator places the participant at
             unacceptable risk if they were to participate in the study or confounds the ability to
             interpret data from the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Duration of response
Time Frame:From the first date at which a partial or complete response is documented until progression or censored at the date of the last Kaposi sarcoma (KS) evaluation during which the participant was determined to still be in response, assessed up to 5 years
Safety Issue:
Description:The Kaplan-Meier (K-M) method will be used to describe duration of response for all treated participants. The cumulative proportion of study participants still in response at one year will be estimated using the point estimate and the 95% confidence interval using Greenwood's formula for the standard error of the K-M estimate. The proportional hazards model will be used to evaluate the association of human immunodeficiency virus (HIV) status and pretreatment status on duration of response.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From the date of enrollment to the date of progression or death (whichever comes first) or censored at the time the participant was last known to be alive without progression, assessed up to 5 years
Safety Issue:
Description:The K-M method will be used to describe progression-free survival; estimates including median and 95% confidence intervals will be provided. The proportional hazards method will be used to evaluate the association of HIV status and pretreatment status on progression-free survival.
Measure:Overall response rate (ORR)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:The binomial proportion and its 95% confidence interval will be used to estimate ORR in four groups defined by HIV status and pretreatment status (HIV+, pretreated), (HIV+, treatment naive), (HIV-, pretreated) and (HIV-, treatment naive. In addition, the binomial proportion and its 95% confidence interval will be used to describe the ORR for HIV+ and HIV- participants, and those that were pretreated and treatment naïve.
Measure:Incidence of adverse events
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will be assessed using version Common Terminology Criteria for Adverse Events 5.0. Adverse events observed on this study will be summarized by organ system, severity grade and relationship to pomalidomide. Frequency and severity of adverse events will be tabulated at the event and person level.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

October 6, 2020