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A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Sarcoma, Kaposi

Thank you

Trial Information

A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV


Background:

Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most
frequently involves the skin. It is seen most frequently in people with HIV or other forms
of immune compromise. Current therapies are limited by toxicities, including cumulative
cardiotoxicity, while effective oral agents, agents deliverable in resource-limited
settings, and agents deliverable long-term for relapsing disease are all lacking.

Objectives:

The primary objective of this study is to:

Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi
sarcoma, whether HIV associated or not.

Eligibility:

- Age greater than or equal to 18 years

- Measurable, pathologically confirmed KS

- Any HIV status; HIV-associated KS subjects must be receiving and able to comply with
HAART and have achieved an HIV viral load < 10,000 copies/mL

- Hematologic and biochemical parameters within prespecified limits at baseline

- Willing to use effective birth control, as defined in the full protocol

- For subjects enrolled in the anti-tumor activity assessment phase, if KS is
HIV-associated it must be increasing despite HAART and HIV suppression for greater than
or equal to 2months, or stable despite HAART for greater than or equal to 3months

- No symptomatic pulmonary or visceral KS

- No specific KS therapy within 4 weeks (6 weeks if that therapy was bevacizumab)

- Neither pregnant nor breast feeding

Design:

This is an open label single agent phase I/II study of pomalidomide in patients with KS. In
the phase I portion, up to six subjects will initially be treated with pomalidomide 5mg
daily for 21 days of a 28 day cycle. Subject to toxicity evaluation, this dosage may be
deescalated to 3mg daily for 21 days of a 28 day cycle in a second cohort of up to six
subjects. If either dose proves tolerable, the study will proceed to the phase II portion,
and additional subjects to a goal of 15 HIV positive and 10 HIV negative subjects evaluable
for response will be added at the highest tolerable dose to gain preliminary information on
activity.

Inclusion Criteria


- INCLUSION CRITERIA:

- Age greater than or equal to 18 Years.

- Any HIV status.

- Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center,
National Institutes of Health.

- At least five measurable KS lesions with no previous local radiation, surgical or
intralesional cytotoxic therapy that would prevent response

assessment for that lesion.

- 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 HAART regimen consistent with current
clinical guidelines.

- Must have been receiving HAART for at least one month.

- Must have achieved an HIV 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/mm3

- The following biochemical parameters:

- Estimated or measured creatinine clearance > 60mL/minute

- Serum alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit
of normal

- Serum aspartate aminotransferase (AST) less than or equal to 2.5 times upper
limit of normal

- Bilirubin less than or equal to 1.5 times upper limit of normal unless the
patient is receiving protease inhibitor therapy (e.g. indinavir, ritonavir,
nelfinavir, or atazanavir) known to be associated with increased bilirubin, in
which case total bilirubin less than or equal to 7.5 mg/dL with direct fraction
<= less than or equal to 0.7 mg/dL.

- 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. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable
Birth Control Methods, and also

- Education and Counseling Guidance Document.

- 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).

- Willing and able to give informed consent.

- For subjects with HIV-associated entered after a tolerable dose has been determined,
KS lesions must be either:

- Increasing despite HAART and HIV suppression below the limit of detection (48
copies/mL) in the two months prior to screening or

- Stable despite HAART for at least three months. Stable disease must be
symptomatic (examples of symptomatic disease include disease associated with
pain, edema, psychological distress and/or social withdrawal). This is to gain
preliminary information about pomalidomide activity without confounding due to
HAART initiation.

EXCLUSION CRITERIA:

- 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 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

- Asymptomatic hyperuricemia, hypophosphatemia, or creatine kinase (CK) Elevations

- Direct manifestations of KS

- Direct manifestations of HIV infection, except for neurologic or cardiac
manifestations

- Direct manifestations of HIV therapy, except for neurologic or cardiac
manifestations.

- History of venous or arterial thromboembolism, unless:

-- Line-related thrombosis without embolus occurring greater than or equal to 1 year
prior to screening.

- Known procoagulant disorder including prothrombin gene mutation 20210, antithrombin
III deficiency, protein C deficiency, protein S deficiency and 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.

- Pregnancy.

- Breast feeding (if lactating, must agree not to breast feed while taking
pomalidomide).

- Prior therapy with pomalidomide.

- Known hypersensitivity to thalidomide, lenalidomide or pomalidomide. including prior
development of erythema nodosum if characterized by a desquamating rash while taking
thalidomide, lenalidomide or pomalidomide.

- Any condition, including the presence of laboratory abnormalities, which in the
opinion of the Principal Investigator or Lead Associate Investigator places the
subject at unacceptable risk if they were to participate in the study or confounds
the ability to interpret data from the study.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not, at a dose derived from solid tumor studies.

Outcome Time Frame:

6 -12 months

Principal Investigator

Robert Yarchoan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

120047

NCT ID:

NCT01495598

Start Date:

December 2011

Completion Date:

December 2014

Related Keywords:

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

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892