AIDS, HIV Positive, Kaposi's Sarcoma
Conditions
Keywords
HIV positive, AIDS, Kaposi's sarcoma, Sarcoma, tumor, cancer
Brief summary
This is a pilot study to determine the efficacy, kinetics and safety of aldoxorubicin in HIV positive subjects with Kaposi's sarcoma.
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.
Interventions
DRUG50 mg/m2 aldoxorubicin
DRUG100 mg/m2 aldoxorubicin
DRUG150 mg/m2 aldoxorubicin
Sponsors
ImmunityBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | up to 6 months | 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. |
| Number of Participants With Treatment-related Toxicities (Adverse Events) in This Subject Population | 30 days from last dose, up to 199 days | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 mg/m^2 Aldoxorubicin 50 mg/m\^2 aldoxorubicin | 1 |
| 100 mg/m^2 Aldoxorubicin 100 mg/m\^2 aldoxorubicin | 7 |
| 150 mg/m^2 Aldoxorubicin 150 mg/m\^2 aldoxorubicin | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | 50 mg/m^2 Aldoxorubicin | 100 mg/m^2 Aldoxorubicin | 150 mg/m^2 Aldoxorubicin | Total |
|---|---|---|---|---|
| Age, Continuous | 55.9 years | 36.7 years STANDARD_DEVIATION 10.44 | 38.3 years STANDARD_DEVIATION 10.87 | 38.7 years STANDARD_DEVIATION 10.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 6 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HIV-Infected Patients with Kaposi's Sarcoma | 1 Participants | 7 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 7 | 1 / 7 |
| other Total, other adverse events | 1 / 1 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 1 | 1 / 7 | 3 / 7 |
Outcome results
Primary
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)
Time frame: 30 days from last dose, up to 199 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/m^2 Aldoxorubicin | Number of Participants With Treatment-related Toxicities (Adverse Events) in This Subject Population | 1 Participants |
| 100 mg/m^2 Aldoxorubicin | Number of Participants With Treatment-related Toxicities (Adverse Events) in This Subject Population | 6 Participants |
| 150 mg/m^2 Aldoxorubicin | Number of Participants With Treatment-related Toxicities (Adverse Events) in This Subject Population | 6 Participants |
Primary
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.
Time frame: up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg/m^2 Aldoxorubicin | Objective Response Rate | 0 Participants |
| 100 mg/m^2 Aldoxorubicin | Objective Response Rate | 7 Participants |
| 150 mg/m^2 Aldoxorubicin | Objective Response Rate | 6 Participants |