A Study to Investigate ALDOXORUBICIN in HIV-infected Subjects With Kaposi's Sarcoma

Study Overview
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Brief Summary
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This is a pilot study to determine the efficacy, kinetics and safety of aldoxorubicin in HIV positive subjects with Kaposi's sarcoma.

Detailed Description
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This is an open-label pilot phase 2 study to investigate efficacy, safety, and intratumoral kinetics of aldoxorubicin in HIV-Infected patients with Kaposi's sarcoma.

Official Title
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An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of ALDOXORUBICIN in HIV-Infected Patients With Kaposi's Sarcoma

Conditions
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Kaposi's Sarcoma, HIV Positive, AIDS

Intervention / Treatment
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* Drug: aldoxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years of age; male or female. HIV (confirmed by ELISA and western blot) with histologically confirmed KS. Willing to undergo serial tumor biopsies. Capable of providing informed consent and complying with trial procedures. KPS ≥70 (Appendix B) Easter Cooperative Oncology Group (ECOG) PS 0-2. Life expectancy ≥ 8 weeks. Measurable (at accessible site or radiographic) tumor lesions according to ACTG TIS criteria. Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.) Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Geographic accessibility to the site. Exclusion Criteria: Prior exposure to an anthracycline. Surgery and/or radiation treatment < 4 weeks prior to Randomization. Exposure to any investigational agent within 30 days of Randomization. History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥3 years. Laboratory values: Screening serum creatinine >1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) > 2.5 × ULN, total bilirubin >1.5 × ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <75,000/mm3, absolute lymphocyte count <1000/mm3, hematocrit level <25% for females or <27% for males, serum albumin ≤2.5 g/dL. Evidence of central nervous system (CNS) hemorrhage National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (published 28 May 2009) grade 2 or greater on baseline MRI. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association (NYHA) guidelines. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V. History or signs of active coronary artery disease with or without angina pectoris. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular ejection fraction (LVEF) <45% of predicted institutional normal value. Active, clinically significant serious infection requiring treatment with antibacterial, antiviral (other than antiretroviral therapy), or antifungal therapy. Major surgery within 4 weeks prior to Randomization. Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results. Any condition that is unstable and could jeopardize the subject's participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aldoxorubicin<br>Subjects will receive either 100 or 150 mg/m2 (75, and 110 mg/m2 doxorubicin equivalents) by intravenous infusion (IVI) to 10 subjects in each group. | Drug: aldoxorubicin<br> <br> * Other names: INNO-206;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | To evaluate the uptake of aldoxorubicin into the tumor and the objective response rate (complete and partial response) using RECIST 1.1 criteria in subjects with HIV-infected with Kaposi's sarcoma | up to 6 months | 
| Safety | To evaluate the safety of ALDOXORUBICIN in this population, assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiogram (ECHO) evaluations, electrocardiogram (ECG) results, and weight. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics | To evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression through sequential biopsies of KS skin lesions. | up to 6 months | 
| Performance Status | To determine the change in performance status (PS) as measured by the Karnofsky Performance Status (KPS). | up to 6 months | 
| Quality of Life | To determine the change in quality of life as measured by the KS Functional Assessment of HIV (FAHI) Quality of Life instrument (QoLI) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV positive, AIDS, Kaposi's sarcoma, Sarcoma, tumor, cancer