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

NCT02659930 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 16004716-C-0047
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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 ...

Conditions

Kaposi Sarcoma

Keywords

HIV; AIDS; Multicentric Castleman Disease

Outcome Measures

Primary Outcomes (2)

• safety/tolerability of dose combinations

  Incidence of dose limiting toxicity and emerging adverse events

  3 months

• pharmacokinetics of combination therapy

  Pomalidomide plasma concentrations

  first 3 days of cycle

Secondary Outcomes (3)

• Quality of life

  3 months

• pulmonary function

  baseline, cycle 2 and at the end of study

• PET

  3 months

Study Arms (4)

1/Group I

EXPERIMENTAL

Pomalidomide and liposomal doxorubicin given at escalating doses to patients with KS requiring systemic therapy

Drug: liposomal doxorubicin; Drug: pomalidomide

2/Group I; Antitumor Assessment Phase

EXPERIMENTAL

Pomalidomide and liposomal doxorubicin, given at the highest tolerated dose to patients with KS requiring systemic therapy

Drug: liposomal doxorubicin; Drug: pomalidomide

3/Group II

EXPERIMENTAL

Pomalidomide with liposomal doxorubicin given at escalating doses in to patients with advanced KS or KS and concurrent KSHV-associated MCD or KICS requiring systemic therapy

Drug: liposomal doxorubicin; Drug: pomalidomide

4/Group II; Antitumor Assessment Phase

EXPERIMENTAL

Pomalidomide and liposomal doxorubicin, given at the highest tolerated dose to patients with KS or KS with concurrent KSHV-associated MCD or KICS requiring systemic therapy

Drug: liposomal doxorubicin; Drug: pomalidomide

Interventions

liposomal doxorubicin DRUG

liposomal doxorubicin IV day 1 of a 28-day cycle

1/Group I; 2/Group I; Antitumor Assessment Phase; 3/Group II; 4/Group II; Antitumor Assessment Phase

pomalidomide DRUG

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

1/Group I; 2/Group I; Antitumor Assessment Phase; 3/Group II; 4/Group II; Antitumor Assessment Phase

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome; Multi-centric Castleman's Disease

Interventions

liposomal doxorubicin; 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; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Ramya M Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 21, 2016
• Study Start: January 13, 2016
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-02-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@-Genomic data are made available via dbGaP through requests to the data custodians

Locations

US (1)