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

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

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

Study Overview

• Status: Completed
• Conditions: Kaposi's Sarcoma; AIDS; HIV Positive
• Intervention / Treatment: Drug: 50 mg/m2 aldoxorubicin; Drug: 100 mg/m2 aldoxorubicin; Drug: 150 mg/m2 aldoxorubicin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years of age; male or female.
2. HIV (confirmed by ELISA and western blot) with histologically confirmed KS.
3. Willing to undergo serial tumor biopsies.
4. Capable of providing informed consent and complying with trial procedures.
5. KPS ≥70 (Appendix B)
6. Easter Cooperative Oncology Group (ECOG) PS 0-2.
7. Life expectancy ≥ 8 weeks.
8. Measurable (at accessible site or radiographic) tumor lesions according to ACTG TIS criteria.
9. 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.)
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
11. Geographic accessibility to the site.

Exclusion Criteria:

1. Prior exposure to an anthracycline.
2. Surgery and/or radiation treatment < 4 weeks prior to Randomization.
3. Exposure to any investigational agent within 30 days of Randomization.
4. 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.
5. 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.
6. 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.
7. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association (NYHA) guidelines.
8. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
9. History or signs of active coronary artery disease with or without angina pectoris.
10. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular ejection fraction (LVEF) <45% of predicted institutional normal value.
11. Active, clinically significant serious infection requiring treatment with antibacterial, antiviral (other than antiretroviral therapy), or antifungal therapy.
12. Major surgery within 4 weeks prior to Randomization.
13. Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
14. Any condition that is unstable and could jeopardize the subject's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg/m2 aldoxorubicin	Drug: 50 mg/m2 aldoxorubicin
Experimental: 100 mg/m2 aldoxorubicin	Drug: 100 mg/m2 aldoxorubicin
Experimental: 150 mg/m2 aldoxorubicin	Drug: 150 mg/m2 aldoxorubicin

What is the study measuring?

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. Objective responses will be evaluated using the RECIST 1.1 criteria. Changes (i.e. improvements) in tumor measurements from baseline values will be assigned a status of CR or PR or SD. Objective response measurements will comprise the sum of CR plus PR. Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm). Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesions, from the baseline sum longest diameter.	up to 6 months
Number of Participants With Treatment-related Toxicities (Adverse Events) in This Subject Population	All subjects who receive any amount of ALDOXORUBICIN will be included in the safety analyses, which will include the following: The incidence, severity, duration, causality, seriousness, and type of AEs and changes in the subject's physical examination, vital signs, and clinical laboratory results.; vitals signs (systolic/diastolic blood pressure, pulse, respiration, temperature, weight, and body surface area); physical examination; laboratory tests (chemistry, hematology, urinalysis, anion gap)	30 days from last dose, up to 199 days

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

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2014
• Primary Completion (Actual): April 25, 2016
• Study Completion (Actual): April 25, 2016

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 6, 2014
• First Posted (Estimated): January 7, 2014

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: cancer; HIV positive; AIDS; Sarcoma; Kaposi's sarcoma; tumor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; DNA Virus Infections; Herpesviridae Infections; Neoplasms, Vascular Tissue; HIV Infections; Urogenital Diseases; Genital Diseases; Sarcoma; HIV Seropositivity; Sarcoma, Kaposi
• Other Study ID Numbers: ALDOXORUBICIN-P2-KS-01