Clinical trial NCT02029430
Conditions: Kaposi's Sarcoma HIV Positive AIDS
Keywords: HIV positive AIDS Kaposi's sarcoma Sarcoma tumor cancer
Sponsor: ImmunityBio, Inc.
Start date: 2014-04-03; Completion date: 2016-04-25
Enrollment: 15 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: 50 mg/m2 aldoxorubicin intervention 2: 100 mg/m2 aldoxorubicin intervention 3: 150 mg/m2 aldoxorubicin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate Efficacy, Safety, and Intratumoral 
Kinetics of ALDOXORUBICIN in HIV-Infected 
Patients with Kaposi’s Sarcoma  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-KS-01 
STUDY DRUG: 
ALDOXORUBICIN 
IND NUMBER: 
113,695 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
1-310-674-6711
SAFETY FAX: 
1-310-826-6139
DATE OF PROTOCOL: 
December 02, 2013 
CONFIDENTIAL
The information contained in this document is confidential and the proprietary property of CytRx 
Corporation. Any unauthorized use or disclosure of such information without the prior written 
authorization of CytRx Corporation is prohibited. 


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of 
ALDOXORUBICIN in HIV-Infected Patients with Kaposi’s Sarcoma 
Primary Objectives: 
1. Determine the preliminary efficacy of administration of ALDOXORUBICIN for HIV-infected 
patients with Kaposi’s Sarcoma (KS).  
2. 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. 
 
Secondary Objectives: 
1. Evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression 
through sequential biopsies of KS skin lesions. 
2. Determine the change in performance status (PS) as measured by the Karnofsky 
Performance Status (KPS) (Appendix B).   
Study Rationale and Significance: 
ALDOXORUBICIN is a novel prodrug that binds covalently to albumin in the circulation. The drug is 
accumulated in tumors and doxorubicin is released in the tumor by cleaving the acid labile linker 
(EMCH) in the low pH tumor environment.  This carrier-linked pro-drug has demonstrated enhanced 
antitumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
KS remains the most common HIV-associated tumor worldwide. Liposomal doxorubicin represents 
the standard of care for severe dermatologic/systemic KS, but a significant portion, if not the majority, 
of patients exhibit minimal to no clinical response to this agent, especially those with visceral disease, 
poor immune status at the time of therapy, and a history of HIV-associated opportunistic infections 
(OIs). The acidic tumor microenvironment of KS lesions is suitable for cleavage of the acid labile 
linker of ALDOXORUBICIN. Furthermore, minimal to no hematologic toxicities have been 
demonstrated for ALDOXORUBICIN in Phase 1 trials at doses equivalent to and exceeding the dose 
for liposomal doxorubicin recommended for KS treatment (27 mg/m2 for ALDOXORUBICIN, 
equivalent to 20 mg/m2 liposomal doxorubicin). Given the large number of skin lesions typically 
exhibited by HIV+ patients with KS, with or without systemic disease, longitudinal analyses of 
intratumoral drug concentrations and biomarker expression are also feasible.  


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is an open-label phase 2 pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at 50, 100 or 150 mg/m2 (37, 75, and 110 mg/m2 doxorubicin 
equivalents) by intravenous infusion (IVI) to 10 patients in each group. Patients will receive 
ALDOXORUBICIN on Day 1, then every 3 weeks until evidence of tumor progression, unacceptable 
toxicity or withdrawal of consent.  
Staging will be assessed at screening, then every even cycle using the AIDS Clinical Trials Group 
(ACTG) tumor, immune system, systemic illness (TIS) criteria (Appendix G), and treatment will 
continue every 3 weeks until tumor progression is observed, unacceptable toxicity occurs, or consent 
is withdrawn. Response to therapy will be determined through evaluation of skin lesions (number, 
size, and nodularity). Chest computed tomography (CT) and abdominal magnetic resonance imaging 
(MRI) will be performed at baseline, prior to Cycle 4 and at end of treatment to evaluate visceral 
lesions. Subjects will visit the LSU Clinical and Translational Research Center every 3 weeks for their 
IVIs, at which time safety monitoring (including AEs) a directed physical examination, laboratory 
evaluations (serum chemistries, complete blood count [CBC], and urinalysis), vital signs, weight, KPS 
(Appendix B), ECHO evaluations, and ECGs will be performed.   


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Population and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
Subjects must meet the following criteria to be included in the study: 
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 
(Appendix G). 
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: 
Subjects meeting the following criteria will not be enrolled: 
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) 
(Appendix C) 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. 


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Number of Subjects: 
Up to 30 subjects will be enrolled (10 in each arm) at the Louisiana State University (LSU) Health 
Science Center in New Orleans, LA. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50% ethanol: 50% water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IVI in Lactated Ringer’s solution.  Total doses of either 50, 100, or 150 
mg/m2 will be administered at infusion visits. 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
• The following efficacy variables will be evaluated every even cycle: 
1. Tumor staging (ACTG TIS criteria [Appendix G]) 
2. Number of skin lesions (if applicable) 
3. Size of individual skin lesions (if applicable) 
4. Nodularity of skin lesions (if applicable) 
• Chest CT and abdominal MRI will be performed at baseline, prior to Cycle 4 and at end of treatment 
to evaluate visceral lesions. 
 
Safety: 
The following safety variables will be assessed over the course of the study: 
• AEs 
• Ability to remain on assigned treatment (tolerability) 
• Clinical and laboratory data including physical examinations, vital signs, weight, ECHO evaluations, 
ECG results and laboratory test results 
• Use of concomitant medications 
Tumor Pathology: 
The following pathologic variables will be assessed over the course of the study: 
• Concentration of drug within skin tumors and adjacent normal skin will be assessed using HPLC in 
the laboratory of Dr. Om Prakash in the Louisiana Cancer Research Center.  
• Routine histopathologic assessments and expression of KSHV-encoded LANA, secreted protein 
acidic and rich in cysteine (SPARC), gp60, and caveolin (which may relate to mechanisms of drug 
activity) within skin tumors will be assessed by Dr. Luis Del Valle in the Molecular and Histology 
Core Facility in the Louisiana Cancer Research Center. Expression will be assessed quantitatively 
using immunofluorescence analyses and fluorescence intensity quantification software.  
(Appendix F). 


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Statistical Methods: 
In accordance with the intention-to-treat principle, all randomized subjects who enter active treatment 
and have had at least 1 dose of study medication and 1 post-dose efficacy measurement will be 
included in the primary statistical analyses.   
Safety:  
The safety data will be summarized for all subjects. Total number of AEs leading to withdrawal, and 
abnormal laboratory tests will be evaluated. AEs, ability to remain on assigned treatment (tolerability), 
and abnormal findings on physical examinations, vital signs, weight, ECHO evaluations, ECG results, 
laboratory test results, and use of concomitant medications, will be assessed to characterize the 
safety profile of the treatment regimen. Descriptive evaluation denoting the changes from baseline to 
the final assessment visit with respect to key laboratory parameters and vital signs will also be 
provided. 


ALDOXORUBICIN-P2-KS-01 
December 02, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 45 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening
-21 Days 
Cycle 1 All Other 
Cycles 
Cycle 4
Every Odd 
Cycle 
Every Even 
Cycle 
End of Study or 
Early Termination 
Follow-
up12 
Signed informed consent 
X 
 
 
 
 
 
 
 
Review inclusion/exclusion 
 
X 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
 
 
 
 
BSA calculation 
 
X2 
X2 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
 
 
X 
 
KPS 
X 
X 
X 
 
 
 
X 
 
Tumor measurements4 
X16 
 
 
X8 
 
 
X8
 
ECG 
X 
X 
 
X 
 
X15 
 
ECHO (with ejection fraction) 
X 
 
X11 
 
 
X 
 
CBC w/differential & plts5 
X 
X 
X 
 
 
 
X 
 
Serum chemistries5,6  
X 
X 
X 
 
 
 
X 
 
Urinalysis7 
X 
 
 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
ALDOXORUBICIN 
administration14 
 
X 
X 
 
 
 
 
 
Concomitant medications9 
X 
X 
X 
 
 
 
X 
 
Biopsy of tumor 
 
 
 
 
 
X13 
 
 
AEs10 
X 
X 
X 
 
 
 
X 
 
Telephone follow-up12 
 
 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (Section 5 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate Efficacy, Safety, and Intratumoral 
Kinetics of ALDOXORUBICIN in HIV-Infected 
Patients with Kaposi’s Sarcoma  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-KS-01 
STUDY DRUG: 
ALDOXORUBICIN 
IND NUMBER: 
113,695 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
1-310-674-6711
SAFETY FAX: 
1-310-826-6139
ORIGINAL PROTOCOL: 
December 02, 2013 
AMENDMENT 1: 
February 05, 2014 
CONFIDENTIAL 
The information contained in this document is confidential and the proprietary property of CytRx 
Corporation. Any unauthorized use or disclosure of such information without the prior written 
authorization of CytRx Corporation is prohibited. 


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of 
ALDOXORUBICIN in HIV-Infected Patients with Kaposi’s Sarcoma 
Primary Objectives: 
1. Determine the preliminary efficacy of administration of ALDOXORUBICIN for HIV-infected 
patients with Kaposi’s Sarcoma (KS).  
2. 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. 
 
Secondary Objectives: 
1. Evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression 
through sequential biopsies of KS skin lesions. 
2. Determine the change in performance status (PS) as measured by the Karnofsky 
Performance Status (KPS) (Appendix B).   
Study Rationale and Significance: 
ALDOXORUBICIN is a novel prodrug that binds covalently to albumin in the circulation. The drug is 
accumulated in tumors and doxorubicin is released in the tumor by cleaving the acid labile linker 
(EMCH) in the low pH tumor environment.  This carrier-linked pro-drug has demonstrated enhanced 
antitumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
KS remains the most common HIV-associated tumor worldwide. Liposomal doxorubicin represents 
the standard of care for severe dermatologic/systemic KS, but a significant portion, if not the majority, 
of patients exhibit minimal to no clinical response to this agent, especially those with visceral disease, 
poor immune status at the time of therapy, and a history of HIV-associated opportunistic infections 
(OIs). The acidic tumor microenvironment of KS lesions is suitable for cleavage of the acid labile 
linker of ALDOXORUBICIN. Furthermore, minimal to no hematologic toxicities have been 
demonstrated for ALDOXORUBICIN in Phase 1 trials at doses equivalent to and exceeding the dose 
for liposomal doxorubicin recommended for KS treatment (27 mg/m2 for ALDOXORUBICIN, 
equivalent to 20 mg/m2 liposomal doxorubicin). Given the large number of skin lesions typically 
exhibited by HIV+ patients with KS, with or without systemic disease, longitudinal analyses of 
intratumoral drug concentrations and biomarker expression are also feasible.  


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is an open-label phase 2 pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at 50, 100 or 150 mg/m2 (37, 75, and 110 mg/m2 doxorubicin 
equivalents) by intravenous infusion (IVI) to 10 patients in each group. Patients will receive 
ALDOXORUBICIN on Day 1, then every 3 weeks until evidence of tumor progression, unacceptable 
toxicity or withdrawal of consent.  
Staging will be assessed at screening, then every even cycle using the AIDS Clinical Trials Group 
(ACTG) tumor, immune system, systemic illness (TIS) criteria (Appendix G), and treatment will 
continue every 3 weeks until tumor progression is observed, unacceptable toxicity occurs, or consent 
is withdrawn. Response to therapy will be determined through evaluation of skin lesions (number, 
size, and nodularity). Chest computed tomography (CT) and abdominal magnetic resonance imaging 
(MRI) will be performed at baseline, prior to Cycle 4 and at end of treatment to evaluate visceral 
lesions. Subjects will visit the LSU Clinical and Translational Research Center every 3 weeks for their 
IVIs, at which time safety monitoring (including AEs) a directed physical examination, laboratory 
evaluations (serum chemistries, complete blood count [CBC], and urinalysis), vital signs, weight, KPS 
(Appendix B), ECHO evaluations, and ECGs will be performed.   


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Population and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
Subjects must meet the following criteria to be included in the study: 
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 
(Appendix G). 
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: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure > 120 mg/m2 of pegylated liposomal doxorubicin (Doxil). 
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) 
(Appendix C) 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. 


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Number of Subjects: 
Up to 30 subjects will be enrolled (10 in each arm) at the Louisiana State University (LSU) Health 
Science Center in New Orleans, LA. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50% ethanol: 50% water, administration completed within 2 hours (of being 
reconstituted) as a 15-minute IVI at the 50 mg/m2 dose or 30-minute IVI at the 100 or 150 mg/m2 
dose in Lactated Ringer’s solution.  Total doses of either 50, 100, or 150 mg/m2 will be administered 
at infusion visits. 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
 The following efficacy variables will be evaluated every even cycle: 
1. Tumor staging (ACTG TIS criteria [Appendix G]) 
2. Number of skin lesions (if applicable) 
3. Size of individual skin lesions (if applicable) 
4. Nodularity of skin lesions (if applicable) 
 Chest CT and abdominal MRI will be performed at baseline, prior to Cycle 4 and at end of treatment 
to evaluate visceral lesions. 
 
Safety: 
The following safety variables will be assessed over the course of the study: 
 AEs 
 Ability to remain on assigned treatment (tolerability) 
 Clinical and laboratory data including physical examinations, vital signs, weight, ECHO evaluations, 
ECG results and laboratory test results 
 Use of concomitant medications 
Tumor Pathology: 
The following pathologic variables will be assessed over the course of the study: 
 Concentration of drug within skin tumors and adjacent normal skin will be assessed using HPLC in 
the laboratory of Dr. Om Prakash in the Louisiana Cancer Research Center.  
 Routine histopathologic assessments and expression of KSHV-encoded LANA, secreted protein 
acidic and rich in cysteine (SPARC), gp60, and caveolin (which may relate to mechanisms of drug 
activity) within skin tumors will be assessed by Dr. Luis Del Valle in the Molecular and Histology 
Core Facility in the Louisiana Cancer Research Center. Expression will be assessed quantitatively 
using immunofluorescence analyses and fluorescence intensity quantification software.  
(Appendix F). 


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Statistical Methods: 
In accordance with the intention-to-treat principle, all randomized subjects who enter active treatment 
and have had at least 1 dose of study medication and 1 post-dose efficacy measurement will be 
included in the primary statistical analyses.   
Safety:  
The safety data will be summarized for all subjects. Total number of AEs leading to withdrawal, and 
abnormal laboratory tests will be evaluated. AEs, ability to remain on assigned treatment (tolerability), 
and abnormal findings on physical examinations, vital signs, weight, ECHO evaluations, ECG results, 
laboratory test results, and use of concomitant medications, will be assessed to characterize the 
safety profile of the treatment regimen. Descriptive evaluation denoting the changes from baseline to 
the final assessment visit with respect to key laboratory parameters and vital signs will also be 
provided. 


ALDOXORUBICIN-P2-KS-01 Amendment 1 
February 05, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 45 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Cycle 4 
Every Odd 
Cycle 
Every Even 
Cycle 
End of Study or 
Early Termination 
Follow-
up12 
Signed informed consent 
X 
 
 
 
 
 
 
 
Review inclusion/exclusion 
 
X 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
 
 
 
 
BSA calculation 
 
X2 
X2 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
 
 
X 
 
KPS 
X 
X 
X 
 
 
 
X 
 
Tumor measurements4 
X16 
 
 
X8 
 
 
X8 
 
ECG 
X 
X 
 
 
X 
 
X15 
 
ECHO (with ejection fraction) 
X 
 
 
X11 
 
 
X 
 
CBC w/differential & plts5 
X 
X 
X 
 
 
 
X 
 
Serum chemistries5,6  
X 
X 
X 
 
 
 
X 
 
Urinalysis7 
X 
 
 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
ALDOXORUBICIN 
administration14 
 
X 
X 
 
 
 
 
 
Concomitant medications9 
X 
X 
X 
 
 
 
X 
 
Biopsy of tumor 
 
 
 
 
 
X13 
 
 
AEs10 
X 
X 
X 
 
 
 
X 
 
Telephone follow-up12 
 
 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (Section 5 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate Efficacy, Safety, and Intratumoral 
Kinetics of ALDOXORUBICIN in HIV-Infected 
Patients with Kaposi’s Sarcoma  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-KS-01 
STUDY DRUG: 
ALDOXORUBICIN 
IND NUMBER: 
113,695 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
1-310-674-6711
SAFETY FAX: 
1-310-826-6139
ORIGINAL PROTOCOL: 
December 02, 2013 
AMENDMENT 1: 
February 05, 2014 
AMENDMENT 2: 
April 07, 2014 
CONFIDENTIAL 
The information contained in this document is confidential and the proprietary property of CytRx 
Corporation. Any unauthorized use or disclosure of such information without the prior written 
authorization of CytRx Corporation is prohibited. 


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of 
ALDOXORUBICIN in HIV-Infected Patients with Kaposi’s Sarcoma 
Primary Objectives: 
1. Determine the preliminary efficacy of administration of ALDOXORUBICIN for HIV-infected 
patients with Kaposi’s Sarcoma (KS).  
2. 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. 
Secondary Objectives: 
1. Evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression 
through sequential biopsies of KS skin lesions. 
2. Determine the change in performance status (PS) as measured by the Karnofsky 
Performance Status (KPS) (Appendix B).   
Study Rationale and Significance: 
ALDOXORUBICIN is a novel prodrug that binds covalently to albumin in the circulation. The drug is 
accumulated in tumors and doxorubicin is released in the tumor by cleaving the acid labile linker 
(EMCH) in the low pH tumor environment.  This carrier-linked pro-drug has demonstrated enhanced 
antitumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
KS remains the most common HIV-associated tumor worldwide. Liposomal doxorubicin represents 
the standard of care for severe dermatologic/systemic KS, but a significant portion, if not the majority, 
of patients exhibit minimal to no clinical response to this agent, especially those with visceral disease, 
poor immune status at the time of therapy, and a history of HIV-associated opportunistic infections 
(OIs). The acidic tumor microenvironment of KS lesions is suitable for cleavage of the acid labile 
linker of ALDOXORUBICIN. Furthermore, minimal to no hematologic toxicities have been 
demonstrated for ALDOXORUBICIN in Phase 1 trials at doses equivalent to and exceeding the dose 
for liposomal doxorubicin recommended for KS treatment (27 mg/m2 for ALDOXORUBICIN, 
equivalent to 20 mg/m2 liposomal doxorubicin). Given the large number of skin lesions typically 
exhibited by HIV+ patients with KS, with or without systemic disease, longitudinal analyses of 
intratumoral drug concentrations and biomarker expression are also feasible.  


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is an open-label phase 2 pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at 50, 100 or 150 mg/m2 (37, 75, and 110 mg/m2 doxorubicin 
equivalents) by intravenous infusion (IVI) to 10 patients in each group. Patients will receive 
ALDOXORUBICIN on Day 1, then every 3 weeks until evidence of tumor progression, unacceptable 
toxicity or withdrawal of consent.  
Staging will be assessed at screening, then every even cycle using the AIDS Clinical Trials Group 
(ACTG) tumor, immune system, systemic illness (TIS) criteria (Appendix G), and treatment will 
continue every 3 weeks until tumor progression is observed, unacceptable toxicity occurs, or consent 
is withdrawn. Response to therapy will be determined through evaluation of skin lesions (number, 
size, and nodularity). Chest computed tomography (CT) and abdominal magnetic resonance imaging 
(MRI) will be performed at baseline, prior to Cycle 4 and at end of treatment to evaluate visceral 
lesions. Subjects will visit the LSU Clinical and Translational Research Center every 3 weeks for their 
IVIs, at which time safety monitoring (including AEs) a directed physical examination, laboratory 
evaluations (serum chemistries, complete blood count [CBC], and urinalysis), vital signs, weight, KPS 
(Appendix B), ECHO evaluations, and ECGs will be performed.   


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Population and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
Subjects must meet the following criteria to be included in the study: 
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 
(Appendix G). 
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: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure > 375 mg/m2 of doxorubicin or pegylated liposomal doxorubicin (Doxil). 
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) 
(Appendix C) 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. 


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Number of Subjects: 
Up to 30 subjects will be enrolled (10 in each arm) at the Louisiana State University (LSU) Health 
Science Center in New Orleans, LA. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50% ethanol: 50% water, administration completed within 2 hours (of being 
reconstituted) as a 15-minute IVI at the 50 mg/m2 dose or 30-minute IVI at the 100 or 150 mg/m2 
dose in Lactated Ringer’s solution.  Total doses of either 50, 100, or 150 mg/m2 will be administered 
at infusion visits. 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
• The following efficacy variables will be evaluated every even cycle: 
1. Tumor staging (ACTG TIS criteria [Appendix G]) 
2. Number of skin lesions (if applicable) 
3. Size of individual skin lesions (if applicable) 
4. Nodularity of skin lesions (if applicable) 
• Chest CT and abdominal MRI will be performed at baseline, prior to Cycle 4 and at end of treatment 
to evaluate visceral lesions. 
 
Safety: 
The following safety variables will be assessed over the course of the study: 
• AEs 
• Ability to remain on assigned treatment (tolerability) 
• Clinical and laboratory data including physical examinations, vital signs, weight, ECHO evaluations, 
ECG results and laboratory test results 
• Use of concomitant medications 
Tumor Pathology: 
The following pathologic variables will be assessed over the course of the study: 
• Concentration of drug within skin tumors and adjacent normal skin will be assessed using HPLC in 
the laboratory of Dr. Om Prakash in the Louisiana Cancer Research Center.  
• Routine histopathologic assessments and expression of KSHV-encoded LANA, secreted protein 
acidic and rich in cysteine (SPARC), gp60, and caveolin (which may relate to mechanisms of drug 
activity) within skin tumors will be assessed by Dr. Luis Del Valle in the Molecular and Histology 
Core Facility in the Louisiana Cancer Research Center. Expression will be assessed quantitatively 
using immunofluorescence analyses and fluorescence intensity quantification software.  
(Appendix F). 


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Statistical Methods: 
In accordance with the intention-to-treat principle, all randomized subjects who enter active treatment 
and have had at least 1 dose of study medication and 1 post-dose efficacy measurement will be 
included in the primary statistical analyses.   
Safety:  
The safety data will be summarized for all subjects. Total number of AEs leading to withdrawal, and 
abnormal laboratory tests will be evaluated. AEs, ability to remain on assigned treatment (tolerability), 
and abnormal findings on physical examinations, vital signs, weight, ECHO evaluations, ECG results, 
laboratory test results, and use of concomitant medications, will be assessed to characterize the 
safety profile of the treatment regimen. Descriptive evaluation denoting the changes from baseline to 
the final assessment visit with respect to key laboratory parameters and vital signs will also be 
provided. 


ALDOXORUBICIN-P2-KS-01 Amendment 2 
April 07, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 45 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Cycle 4 
Every Odd 
Cycle 
Every Even 
Cycle 
End of Study or 
Early Termination 
Follow-
up12 
Signed informed consent 
X 
 
 
 
 
 
 
 
Review inclusion/exclusion 
 
X 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
 
 
 
 
BSA calculation 
 
X2 
X2 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
 
 
X 
 
KPS 
X 
X 
X 
 
 
 
X 
 
Tumor measurements4 
X16 
 
 
X8 
 
 
X8 
 
ECG 
X 
X 
 
 
X 
 
X15 
 
ECHO (with ejection fraction) 
X 
 
 
X11 
 
 
X 
 
CBC w/differential & plts5 
X 
X 
X 
 
 
 
X 
 
Serum chemistries5,6  
X 
X 
X 
 
 
 
X 
 
Urinalysis7 
X 
 
 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
ALDOXORUBICIN 
administration14 
 
X 
X 
 
 
 
 
 
Concomitant medications9 
X 
X 
X 
 
 
 
X 
 
Biopsy of tumor 
 
 
 
 
 
X13 
 
 
AEs10 
X 
X 
X 
 
 
 
X 
 
Telephone follow-up12 
 
 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (Section 5 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate Efficacy, Safety, and Intratumoral 
Kinetics of ALDOXORUBICIN in HIV-Infected 
Patients with Kaposi’s Sarcoma  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-KS-01 
STUDY DRUG: 
ALDOXORUBICIN 
IND NUMBER: 
113,695 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
1-310-674-6711
SAFETY FAX: 
1-310-826-6139
ORIGINAL PROTOCOL: 
December 02, 2013 
AMENDMENT 1: 
February 05, 2014 
AMENDMENT 2: 
April 07, 2014 
AMENDMENT 3: 
September 10, 2014 
CONFIDENTIAL 
The information contained in this document is confidential and the proprietary property of CytRx 
Corporation. Any unauthorized use or disclosure of such information without the prior written 
authorization of CytRx Corporation is prohibited. 


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of 
ALDOXORUBICIN in HIV-Infected Patients with Kaposi’s Sarcoma 
Primary Objectives: 
1. Determine the preliminary efficacy of administration of ALDOXORUBICIN for HIV-infected 
patients with Kaposi’s Sarcoma (KS).  
2. 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. 
Secondary Objectives: 
1. Evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression 
through sequential biopsies of KS skin lesions only on samples obtained at LSU Medical 
Center. 
2. Determine the change in performance status (PS) as measured by the Karnofsky 
Performance Status (KPS) (Appendix B).  
3. Determine the change in quality of life as measured by the KS Functional Assessment of HIV 
(FAHI) Quality of Life instrument (QoLI) (Appendix H).  
Study Rationale and Significance: 
ALDOXORUBICIN is a novel prodrug that binds covalently to albumin in the circulation. The drug is 
accumulated in tumors and doxorubicin is released in the tumor by cleaving the acid labile linker 
(EMCH) in the low pH tumor environment.  This carrier-linked pro-drug has demonstrated enhanced 
antitumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
KS remains the most common HIV-associated tumor worldwide. Liposomal doxorubicin represents 
the standard of care for severe dermatologic/systemic KS, but a significant portion, if not the majority, 
of patients exhibit minimal to no clinical response to this agent, especially those with visceral disease, 
poor immune status at the time of therapy, and a history of HIV-associated opportunistic infections 
(OIs). The acidic tumor microenvironment of KS lesions is suitable for cleavage of the acid labile 
linker of ALDOXORUBICIN. Furthermore, minimal to no hematologic toxicities have been 
demonstrated for ALDOXORUBICIN in Phase 1 trials at doses equivalent to and exceeding the dose 
for liposomal doxorubicin recommended for KS treatment (27 mg/m2 for ALDOXORUBICIN, 
equivalent to 20 mg/m2 liposomal doxorubicin). Given the large number of skin lesions typically 
exhibited by HIV+ patients with KS, with or without systemic disease, longitudinal analyses of 
intratumoral drug concentrations and biomarker expression are also feasible.  


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is an open-label phase 2 pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at 100 or 150 mg/m2 (75 and 110 mg/m2 doxorubicin equivalents) by 
intravenous infusion (IVI) to 10 patients in each group. Patients will receive ALDOXORUBICIN on 
Day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of 
consent.  
Staging will be assessed at screening, then every even cycle using the AIDS Clinical Trials Group 
(ACTG) tumor, immune system, systemic illness (TIS) criteria (Appendix G), and treatment will 
continue every 3 weeks until tumor progression is observed, unacceptable toxicity occurs, or consent 
is withdrawn. Response to therapy will be determined through evaluation of skin lesions (number, 
size, and nodularity). Chest computed tomography (CT) and abdominal magnetic resonance imaging 
(MRI) will be performed at baseline, prior to Cycle 4 and at end of treatment to evaluate visceral 
lesions. Subjects will visit the clinical site every 3 weeks for their IVIs, at which time safety monitoring 
(including AEs) a directed physical examination, laboratory evaluations (serum chemistries, complete 
blood count [CBC], and urinalysis), vital signs, weight, KPS (Appendix B), ECHO evaluations, and 
ECGs will be performed.  The FAHI QoLI will be administered at and at every fourth cycle. 


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Population and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
Subjects must meet the following criteria to be included in the study: 
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 
(Appendix G). 
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: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure > 375 mg/m2 of doxorubicin or pegylated liposomal doxorubicin (Doxil). 
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 4.03 (Appendix C) 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. 


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Number of Subjects: 
Up to 20 subjects will be enrolled (10 in each arm) at 2-4 sites in the United States. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50% ethanol: 50% water, administration completed within 2 hours (of being 
reconstituted) as a 30-minute IVI in Lactated Ringer’s solution.  Total doses of 100 or 150 mg/m2 will 
be administered at infusion visits. 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
 The following efficacy variables will be evaluated every even cycle: 
1. Tumor staging (ACTG TIS criteria [Appendix G]) 
2. Number of skin lesions (if applicable) 
3. Size of individual skin lesions (if applicable) 
4. Nodularity of skin lesions (if applicable) 
 Chest CT and abdominal MRI will be performed at baseline, prior to Cycle 4 and at end of treatment 
to evaluate visceral lesions. 
 FAHI QoL Instrument at and every fourth cycle. 
 
Safety: 
The following safety variables will be assessed over the course of the study: 
 AEs 
 Ability to remain on assigned treatment (tolerability) 
 Clinical and laboratory data including physical examinations, vital signs, weight, ECHO evaluations, 
ECG results and laboratory test results 
 Use of concomitant medications 
Tumor Pathology: 
The following pathologic variables will be assessed over the course of the study only in subjects 
enrolled at the Louisiana State University (LSU) Health Science Center: 
 Concentration of drug within skin tumors and adjacent normal skin will be assessed using HPLC in 
the laboratory of Dr. Om Prakash in the Louisiana Cancer Research Center.  
 Routine histopathologic assessments and expression of KSHV-encoded LANA, secreted protein 
acidic and rich in cysteine (SPARC), gp60, and caveolin (which may relate to mechanisms of drug 
activity) within skin tumors will be assessed by Dr. Luis Del Valle in the Molecular and Histology 
Core Facility in the Louisiana Cancer Research Center. Expression will be assessed quantitatively 
using immunofluorescence analyses and fluorescence intensity quantification software.  
(Appendix F). 


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Statistical Methods: 
In accordance with the intention-to-treat principle, all randomized subjects who enter active treatment 
and have had at least 1 dose of study medication and 1 post-dose efficacy measurement will be 
included in the primary statistical analyses.   
Safety:  
The safety data will be summarized for all subjects. Total number of AEs leading to withdrawal, and 
abnormal laboratory tests will be evaluated. AEs, ability to remain on assigned treatment (tolerability), 
and abnormal findings on physical examinations, vital signs, weight, ECHO evaluations, ECG results, 
laboratory test results, and use of concomitant medications, will be assessed to characterize the 
safety profile of the treatment regimen. Descriptive evaluation denoting the changes from baseline to 
the final assessment visit with respect to key laboratory parameters and vital signs will also be 
provided. 


ALDOXORUBICIN-P2-KS-01 Amendment 3 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 45 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Cycle 2 Cycle 4 
Every Odd 
Cycle 
Every 
Fourth 
Cycle 
End of Study or 
Early 
Termination 
Follow-
up12 
Signed informed consent 
X 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
 
X 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
 
 
 
 
 
BSA calculation 
 
X2 
X2 
 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
 
 
 
X 
 
KPS 
X 
X 
X 
 
 
 
 
X 
 
FAHI QoL 
X 
 
 
 
 
 
X 
 
 
Tumor measurements4 
X16 
 
 
 
X8 
 
 
X8 
 
ECG 
X 
X 
 
 
 
X 
 
X15 
 
ECHO (with ejection fraction) 
X 
 
 
 
X11 
 
 
X 
 
CBC w/differential & plts5 
X 
X 
X 
 
 
 
 
X 
 
Serum chemistries5,6  
X 
X 
X 
 
 
 
 
X 
 
Urinalysis7 
X 
 
 
 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
ALDOXORUBICIN 
administration14 
 
X 
X 
 
 
 
 
 
 
Concomitant medications9 
X 
X 
X 
 
 
 
 
X 
 
Biopsy of tumor13 
X 
 
 
X 
 
 
X13 
 
 
AEs10 
X 
X 
X 
 
 
 
 
X 
 
Telephone follow-up12 
 
 
 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (Section 5 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate Efficacy, Safety, and Intratumoral 
Kinetics of ALDOXORUBICIN in HIV-Infected 
Patients with Kaposi’s Sarcoma  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-KS-01 
STUDY DRUG: 
ALDOXORUBICIN 
IND NUMBER: 
113,695 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
1-310-674-6711
SAFETY FAX: 
1-310-826-6139
ORIGINAL PROTOCOL: 
December 02, 2013 
AMENDMENT 1: 
February 05, 2014 
AMENDMENT 2: 
April 07, 2014 
AMENDMENT 3: 
September 10, 2014 
AMENDMENT 4: 
January 13, 2015 
CONFIDENTIAL 
The information contained in this document is confidential and the proprietary property of CytRx 
Corporation. Any unauthorized use or disclosure of such information without the prior written 
authorization of CytRx Corporation is prohibited. 


ALDOXORUBICIN-P2-KS-01 A4 
January 13, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate Efficacy, Safety, and Intratumoral Kinetics of 
ALDOXORUBICIN in HIV-Infected Patients with Kaposi’s Sarcoma 
Primary Objectives: 
1. Determine the preliminary efficacy of administration of ALDOXORUBICIN for HIV-infected 
patients with Kaposi’s Sarcoma (KS).  
2. 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. 
Secondary Objectives: 
1. Evaluate the intratumoral kinetics of ALDOXORUBICIN and related biomarker expression 
through sequential biopsies of KS skin lesions only on samples obtained at LSU Medical 
Center. 
2. Determine the change in performance status (PS) as measured by the Karnofsky 
Performance Status (KPS) (Appendix B).  
3. Determine the change in quality of life as measured by the KS Functional Assessment of HIV 
(FAHI) Quality of Life instrument (QoLI) (Appendix H).  
Study Rationale and Significance: 
ALDOXORUBICIN is a novel prodrug that binds covalently to albumin in the circulation. The drug is 
accumulated in tumors and doxorubicin is released in the tumor by cleaving the acid labile linker 
(EMCH) in the low pH tumor environment.  This carrier-linked pro-drug has demonstrated enhanced 
antitumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
KS remains the most common HIV-associated tumor worldwide. Liposomal doxorubicin represents 
the standard of care for severe dermatologic/systemic KS, but a significant portion, if not the majority, 
of patients exhibit minimal to no clinical response to this agent, especially those with visceral disease, 
poor immune status at the time of therapy, and a history of HIV-associated opportunistic infections 
(OIs). The acidic tumor microenvironment of KS lesions is suitable for cleavage of the acid labile 
linker of ALDOXORUBICIN. Furthermore, minimal to no hematologic toxicities have been 
demonstrated for ALDOXORUBICIN in Phase 1 trials at doses equivalent to and exceeding the dose 
for liposomal doxorubicin recommended for KS treatment (27 mg/m2 for ALDOXORUBICIN, 
equivalent to 20 mg/m2 liposomal doxorubicin). Given the large number of skin lesions typically 
exhibited by HIV+ patients with KS, with or without systemic disease, longitudinal analyses of 
intratumoral drug concentrations and biomarker expression are also feasible.  


ALDOXORUBICIN-P2-KS-01 A4 
January 13, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is an open-label phase 2 pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at 100 or 150 mg/m2 (75 and 110 mg/m2 doxorubicin equivalents) by 
intravenous infusion (IVI) to 10 patients in each group. Patients will receive ALDOXORUBICIN on 
Day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of 
consent.  
Staging will be assessed at screening, then every even cycle using the AIDS Clinical Trials Group 
(ACTG) tumor, immune system, systemic illness (TIS) criteria (Appendix G), and treatment will 
continue every 3 weeks until tumor progression is observed, unacceptable toxicity occurs, or consent 
is withdrawn. Response to therapy will be determined through evaluation of skin lesions (number, 
size, and nodularity). Chest computed tomography (CT) and abdominal magnetic resonance imaging 
(MRI) will be performed at baseline, prior to Cycle 4 and at end of treatment to evaluate visceral 
lesions. Subjects will visit the clinical site every 3 weeks for their IVIs, at which time safety monitoring 
(including AEs) a directed physical examination, laboratory evaluations (serum chemistries and 
complete blood count [CBC]), vital signs, weight, KPS (Appendix B), ECHO evaluations, and ECGs 
will be performed.  All subjects will have blood drawn for serum electrolytes to evaluate the anion gap 
prior to each drug administration. The FAHI QoLI will be administered at and at every fourth cycle. 


ALDOXORUBICIN-P2-KS-01 A4 
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Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Study Population and Main Criteria for Inclusion/Exclusion: 
Inclusion Criteria: 
Subjects must meet the following criteria to be included in the study: 
1. Age ≥18 years of age; male or female. 
2. HIV (confirmed by ELISA, western blot, OraQuick®, or viral loads) 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 
(Appendix G). 
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: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure > 375 mg/m2 of doxorubicin or pegylated liposomal doxorubicin (Doxil). 
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. Anion gap > 16 meq/L or arterial blood pH <7.30. 
7. Evidence of central nervous system (CNS) hemorrhage National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (Appendix C) grade 2 or 
greater on baseline MRI. 
8. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines. 
9. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute 
arrhythmia or ventricular arrhythmias classified as Lown III, IV or V. 
10. History or signs of active coronary artery disease with or without angina pectoris. 
11. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular 
ejection fraction (LVEF) <45% of predicted institutional normal value. 
12. Active, clinically significant serious infection requiring treatment with antibacterial, antiviral (other 
than antiretroviral therapy), or antifungal therapy. 
13. Major surgery within 4 weeks prior to Randomization. 
14. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
15. Any condition that is unstable and could jeopardize the subject’s participation in the study. 


ALDOXORUBICIN-P2-KS-01 A4 
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Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Number of Subjects: 
Up to 20 subjects will be enrolled (10 in each arm) at 2-4 sites in the United States. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50% ethanol: 50% water, administration completed within 2 hours (of being 
reconstituted) as a 30-minute IVI in Lactated Ringer’s solution.  Total doses of 100 or 150 mg/m2 will 
be administered at infusion visits. 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
• The following efficacy variables will be evaluated every even cycle: 
1. Tumor staging (ACTG TIS criteria [Appendix G]) 
2. Number of skin lesions (if applicable) 
3. Size of individual skin lesions (if applicable) 
4. Nodularity of skin lesions (if applicable) 
• Chest CT and abdominal MRI will be performed at baseline, prior to Cycle 4 and at end of treatment 
to evaluate visceral lesions. 
• FAHI QoL Instrument at and every fourth cycle. 
 
Safety: 
The following safety variables will be assessed over the course of the study: 
• AEs 
• Ability to remain on assigned treatment (tolerability) 
• Clinical and laboratory data including physical examinations, vital signs, weight, ECHO evaluations, 
ECG results and laboratory test results 
• Use of concomitant medications 
Tumor Pathology: 
The following pathologic variables will be assessed over the course of the study only in subjects 
enrolled at the Louisiana State University (LSU) Health Science Center: 
• Concentration of drug within skin tumors and adjacent normal skin will be assessed using HPLC in 
the laboratory of Dr. Om Prakash in the Louisiana Cancer Research Center.  
• Routine histopathologic assessments and expression of KSHV-encoded LANA, secreted protein 
acidic and rich in cysteine (SPARC), gp60, and caveolin (which may relate to mechanisms of drug 
activity) within skin tumors will be assessed by Dr. Luis Del Valle in the Molecular and Histology 
Core Facility in the Louisiana Cancer Research Center. Expression will be assessed quantitatively 
using immunofluorescence analyses and fluorescence intensity quantification software.  
(Appendix F). 


ALDOXORUBICIN-P2-KS-01 A4 
January 13, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
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Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-KS-01 
 
Phase of Development: 2 
 
Statistical Methods: 
In accordance with the intention-to-treat principle, all randomized subjects who enter active treatment 
and have had at least 1 dose of study medication and 1 post-dose efficacy measurement will be 
included in the primary statistical analyses.   
Safety:  
The safety data will be summarized for all subjects. Total number of AEs leading to withdrawal, and 
abnormal laboratory tests will be evaluated. AEs, ability to remain on assigned treatment (tolerability), 
and abnormal findings on physical examinations, vital signs, weight, ECHO evaluations, ECG results, 
laboratory test results, and use of concomitant medications, will be assessed to characterize the 
safety profile of the treatment regimen. Descriptive evaluation denoting the changes from baseline to 
the final assessment visit with respect to key laboratory parameters and vital signs will also be 
provided. 


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APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Cycle 2 Cycle 4 
Every Odd 
Cycle 
Every 
Fourth 
Cycle 
End of Study or 
Early 
Termination 
Follow-
up12 
Signed informed consent 
X 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
 
X 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
 
 
 
 
 
BSA calculation 
 
X2 
X2 
 
 
 
 
 
 
Vital signs3 
X 
X 
X 
 
 
 
 
X 
 
KPS 
X 
X 
X 
 
 
 
 
X 
 
FAHI QoL 
X 
 
 
 
 
 
X 
 
 
Tumor measurements4 
X16 
 
 
 
X8 
 
 
X8 
 
ECG 
X 
X 
 
 
 
X 
 
X15 
 
ECHO (with ejection fraction) 
X 
 
 
 
X11 
 
 
X 
 
CBC w/differential & plts5 
X 
X 
X 
 
 
 
 
X 
 
Serum chemistries5,6  
X* 
X 
X 
 
 
 
 
X 
 
Urinalysis7 
X 
 
 
 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
ALDOXORUBICIN 
administration14 
 
X 
X 
 
 
 
 
 
 
Concomitant medications9 
X 
X 
X 
 
 
 
 
X 
 
Biopsy of tumor13 
X 
 
 
X 
 
 
X13 
 
 
AEs10 
X 
X 
X 
 
 
 
 
X 
 
Telephone follow-up12 
 
 
 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (Section 5 for details). 
*Arterial blood gas test, if needed, to confirm acid levels.