Status and phase
Conditions
Treatments
About
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
Full description
Background:
Objectives:
Eligibility:
Patients with biopsy proven (confirmed in the Laboratory of Pathology, CCR) Kaposi sarcoma (KS)
Group I: KS requiring systemic therapy (no prior therapy required)
OR
--KS patients with an inadequate response to pomalidomide (either progressive disease or stable disease after 4 months)
OR
KS patients with an inadequate response to liposomal doxorubicin, paclitaxel, or other systemic chemotherapy (either progressive disease or stable disease after 6 cycles)
Group I will exclude patients eligible for Group II (below).
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 in one of the following high-risk groups (no prior therapy required):
Concurrent KSHV-associated multicentric Castleman disease (MCD)
KSHV Inflammatory Cytokine Syndrome (KICS), including those also meeting clinical criteria for KS immune reconstitution syndrome (KS IRIS)
Patients with primary effusion lymphoma or a large cell lymphoma arising in KSHV-associated MCD are excluded.
Design:
This is a Phase I study evaluating 2 groups of patients with KS. Patients will receive pomalidomide once a day, days 1-21 of a 28-day cycle, at the various dose levels combined with liposomal doxorubicin IV day 1 of a 28-day cycle until optimal tumor response, unacceptable toxicity, or patient request to discontinue
The study will proceed to an antitumor activity phase to assess in a preliminary manner the response of Group I patients to a fixed dose of pomalidomide and liposomal doxorubicin. Up to 30 subjects (HIV positive or negative) evaluable for response will be treated at the highest tolerable combination of pomalidomide and liposomal doxorubicin (determined to be dose level 3: pomalidomide 4mg in combination with 20mg/m^2 liposomal doxorubicin) to gain preliminary information on antitumor activity in an expansion cohort. Based on the observation of positive results in the initial dose expansion of 14 patients evaluated in the expansion cohort, a total of 30 patients will be allowed to be included in this cohort in order to gain additional safety information as well as to improve the precision of the estimate of the response rate in Group I patients.
The study will also include an antitumor activity phase to assess in a preliminary manner the response of Group II patients to a fixed dose of pomalidomide and liposomal doxorubicin. Up to 10 total patients (HIV positive or negative) evaluable for response will be treated at the highest tolerated dose of pomalidomide for this population (determined to be dose level, 2mg in combination with 20mg/m2 liposomal doxorubicin) to gain preliminary information on KS that occurs concurrently with KSHV-MCD or KICS.
This study will also evaluate the characteristics of 18fluoro-thymidine (FLT) positron emission tomography (PET) in patients with KS and concurrent KSHV-associated MCD or KICS, and correlate with markers of KSHV-lytic activation.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion 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 II: KS (no prior therapy required):
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):
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:
Age greater than or equal to 18 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
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:
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:
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.
Primary purpose
Allocation
Interventional model
Masking
62 participants in 4 patient groups
Loading...
Central trial contact
Ramya M Ramaswami, M.D.; Anaida Widell
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal