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Pomalidomide in Combination With Liposomal Doxorubicin in People With Advanced or Refractory Kaposi Sarcoma

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ClinicalTrials.gov Identifier: NCT02659930
Recruitment Status : Recruiting
First Posted : January 21, 2016
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Kaposi sarcoma (KS) is a cancer most often seen in people with HIV. It causes lesions. These are usually on the skin but sometimes in the lymph nodes, lungs, and gastrointestinal tract. Researchers think a combination of drugs may help treat KS.

Objective:

To test a combination of the anti-cancer drugs pomalidomide (CC-4047) and liposomal doxorubicin (Doxil) in people with KS.

Eligibility:

People ages 18 and over with KS

Design:

Participants will be screened with:

Medical history

Questionnaires

Physical exam

Blood, urine, and heart tests

Chest X-ray

Biopsy: A small sample of tissue is taken from a KS lesion.

Possible CT scan

Possible exam of lungs or gastrointestinal tract with an endoscope: A flexible instrument examines

inside the organ.

Participants will take the drugs in 4-week cycles. They will take Doxil through an IV on Day 1 of each cycle. They will take CC-4047 tablets by mouth each day for the first 3 weeks of each cycle.

Participants will have many visits:

Before starting treatment

To start each cycle

Day 15 of first 2 cycles

Visits include repeats of screening tests and:

Multiple blood draws

Photographs of lesions

Participants will keep a drug diary.

Participants will take aspirin or other drugs to prevent blood clots.

Participants with HIV will have combination antiretroviral therapy.

Some participants will have a PET scan.

Participants will continue treatment as long as they tolerate it and their KS improves. After treatment, they will have several follow-up visits for up to 5 years


Condition or disease Intervention/treatment Phase
Kaposi Sarcoma Drug: liposomal doxorubicin Drug: pomalidomide Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 77 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of Pomalidomide in Combination With Liposomal Doxorubicin in Patients With Advanced or Refractory Kaposi Sarcoma
Actual Study Start Date : January 13, 2016
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 30, 2021


Arm Intervention/treatment
Experimental: 1/Group 1
pomalidomide and liposomal doxorubicin in patients with KS requiring systemic therapy
Drug: liposomal doxorubicin
liposomal doxorubicin IV day 1 of a 28-day cycle

Drug: pomalidomide
pomalidomide once a day, days 1- 21 of a 28-day cycle, at the dose levels described in dose escalation plan

Experimental: 2/ Group I; Antitumor Assessment Phase
Pomalidomide and liposomal doxorubicin, given at the highest tolerated dose to patients with KS requiring systemic therapy
Drug: liposomal doxorubicin
liposomal doxorubicin IV day 1 of a 28-day cycle

Drug: pomalidomide
pomalidomide once a day, days 1- 21 of a 28-day cycle, at the dose levels described in dose escalation plan

Experimental: 3/Group II
pomalidomide with liposomal doxorubicin in patients with advanced KS or KS and concurrent KSHV- associated MCD or KICS
Drug: liposomal doxorubicin
liposomal doxorubicin IV day 1 of a 28-day cycle

Drug: pomalidomide
pomalidomide once a day, days 1- 21 of a 28-day cycle, at the dose levels described in dose escalation plan




Primary Outcome Measures :
  1. safety/tolerability of dose combinations [ Time Frame: 3 months ]
    Incidence of dose limiting toxicity and emerging adverse events

  2. pharmacokinetics of combination therapy [ Time Frame: first 3 days of cycle ]
    Pomalidomide plasma concentrations



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients must have histologically confirmed Kaposi sarcoma (KS) confirmed by the Laboratory of Pathology, NCI.
  • All patients should have either five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion; or other assessable disease
  • Group I: KS requiring systemic therapy (no prior therapy required) and:

    • Group I patients should have one or more of the following:
    • T1 KS, KS on skin sufficiently widespread that it is not amenable to local therapy, or KS affecting quality of life due to local symptoms or psychological distress
    • KS patients with an inadequate response to pomalidomide (either progressive disease or stable disease requiring additional therapy after 4 months)
    • KS patients with an inadequate response to liposomal doxorubicin, paclitaxel, or other systemic chemotherapy (either progressive disease or stable disease requiring additional therapy after 6 cycles)

      • Group I will exclude patients eligible for Group II (below). Patients with a history of multicentric Castleman disease (MCD) in the absence of any active disease (as assessed by the PI) are eligible for Group I.
      • A wash out period off treatment of 3 weeks will be required, except in the case of patients with progressive, severe disease in which delay of treatment cannot be justified (i.e. symptomatic pulmonary KS)
  • Group II: KS (no prior therapy required):

    • Concurrent active KSHV-associated multicentric Castleman disease (MCD)
    • Active KSHV Inflammatory Cytokine Syndrome (KICS), including those also meeting clinical criteria for KS immune reconstitution syndrome (KS IRIS)
  • At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion; or other assessable disease
  • ECOG Performance Status (PS):

    • Group I: less than or equal to 2
    • Group II: less than or equal to 3
    • ECOG PS of 4 will be allowed in Group II only if symptoms due to pulmonary KS. (with Karnofsky = 20%).
  • Measurable disease by the criteria proposed by the AIDS Clinical Trials Group Oncology Committee (for KS).
  • Patients can be HIV positive or negative.
  • HAART for HIV+ patients:

    • All HIV+ patients must be willing to be compliant with HAART
    • Group I-on HAART for 1 month with stable disease; however, no minimum time restriction for patients with progressive and/or end-organ threatening disease
    • Group II-no minimum time restriction on prior HAART, patients may be HAART naive.
  • Age greater than or equal to18 years.

    --Because no dosing or adverse event data are currently available on the use of pomalidomide in combination with liposomal doxorubicin in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.

  • Patients must have normal organ and marrow function as defined below:

    • Absolute neutrophil count greater than or equal to 1,000/mcL
    • Platelets >75,000/mcL
    • Hemoglobin

      • Group I: greater than or equal to 8 gm/dL;
      • Group II: if anemia attributed to KS, KSHV-MCD, or KICS greater than or equal to 7gm/dL, otherwise greater than or equal to 8 gm/dL
    • Total bilirubin less than or equal to1.5 upper limit of normal unless the patient is receiving a protease inhibitor known to be associated with increased bilirubin (e.g. atazanavir), in which case total bilirubin less than or equal to 7.5 mg/dL with direct fraction less than or equal to 0.7
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • Creatinine within normal institutional limits OR Creatinine clearance >60 mL/min/1.73 m(2) as estimated by either Cockroft-Gault or 24-hour urine collection for patients with creatinine levels above institutional normal
  • Cardiac ejection fraction greater than or equal to 50% by echocardiogram
  • Patients with a cumulative lifetime history of anthracycline greater than 430 mg/m(2) are eligible, after consultation with a cardiologist, if there are none of the following cardiac risk factors:

    • Diabetes mellitus
    • History of acute coronary syndrome
    • Hypertension; defined as a sustained systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure greater than 90 mmHg OR use of an antihypertensive medication for the indication of hypertension.
  • All study participants must agree to be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMSTM 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)
  • Because pomalidomide is an agent with the potential for teratogenic or abortifacient effects, 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.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • Patients with primary effusion lymphoma or other concurrent malignancy, except for basal cell carcinoma or squamous carcinoma of the skin or in situ cervical or anal dysplasia
  • History of malignant tumors other than KS or KSHV-MCD, unless:

    • In complete remission for greater than or equal to 1 year for the time complete remission was first documented
    • Resected basal cell or squamous cell carcinoma of the skin
    • In situ cervical or anal dysplasia
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of allergic reactions attributed to thalidomide, lenalidomide, or other compounds of similar chemical or biologic composition to pomalidomide or other agents used in study
  • 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. These potential risks may also

apply to other agents used in this study.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659930


Contacts
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Contact: Anaida Widell (301) 451-3694 awidell@cc.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ramya M Ramaswami, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02659930     History of Changes
Other Study ID Numbers: 160047
16-C-0047
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: December 11, 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
HIV
AIDS
Multicentric Castleman Disease

Additional relevant MeSH terms:
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Sarcoma
Sarcoma, Kaposi
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Vascular Tissue
Doxorubicin
Liposomal doxorubicin
Pomalidomide
Thalidomide
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents