Clinical trial NCT02014844
Conditions: Glioblastoma
Keywords: glioblastoma aldoxorubicin temozolomide brain cancer brain tumor
Sponsor: ImmunityBio, Inc.
Start date: 2014-03-01; Completion date: 2016-12-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a pilot study to determine the efficacy and safety of aldoxorubicin in subjects with glioblastoma who have progressed following surgery and prior treatments.

Detailed description:
This is a second line open-labeled pilot phase 2 study in subjects with glioblastoma whose tumors have progressed following prior treatment with surgery, radiation and Temozolomide. Patients who have received avastin as a second-line treatment are not eligible for this study.

Arms: arm 1: Subjects received 250 mg/m2 aldoxorubicin IV. arm 2: Subjects received 350 mg/m2 aldoxorubicin IV.
Interventions: intervention 1: 250 mg/m2 aldoxorubicin intervention 2: 350 mg/m2 aldoxorubicin
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate the Preliminary Efficacy and 
Safety of Aldoxorubicin in Subjects with 
Unresectable Glioblastoma Whose Tumors 
Have Progressed Following Prior Treatment 
with Surgery, Radiation and Temozolomide  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-GBM-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
119437 
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: 
August 9, 2013 
AMENDMENT 1: 
November 12, 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-GBM-01 Amendment 1                         
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of 
Aldoxorubicin in Subjects with Unresectable Glioblastoma  Whose Tumors Have Progressed 
Following Prior Treatment with Surgery, Radiation and Temozolomide  
Primary Objectives: 
The primary objective of this study is to determine the preliminary efficacy of administration of 
ALDOXORUBICIN to subjects with unresectable glioblastoma (GBM) whose tumors have progressed 
following prior treatment with surgery, radiation and temozolomide, as measured by PFS according to 
the Response Assessment in Neuro-Oncology (RANO) Working Group Criteria (see Appendix F) and 
OS.  
Secondary Objectives: 
The secondary objectives of this study are 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, weight, and the change in performance status as measured by the 
Karnofsky Performance Scale. 
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 prodrug has demonstrated enhanced 
anti-tumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
Patients with unresectable GBM who have failed prior surgery, radiation and chemotherapy with 
temozolomide regimens and bevacizumab have an extremely poor prognosis with progression-free 
survival (PFS) of around 8 weeks and median overall survival (OS) of approximately 8-16 weeks, 
depending on whether salvage therapy is administered. Recently, we have demonstrated in an 
orthotopic xenograft model of GBM in mice that ALDOXORUBICIN significantly retards the growth of 
the tumor and doubles the survival of animals when compared to treatment with either saline or 
doxorubicin.  We have also shown that this molecule collects inside the tumor and not in normal brain 
parenchyma. Doxorubicin does not penetrate into either the tumor or the brain. Thus, 
ALDOXORUBICIN may be able to effectively treat patients with advanced GBM that have progressed 
after standard therapies. 


ALDOXORUBICIN-P2-GBM-01 Amendment 1                         
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or  
250 mg/m2 (185 mg/m2 doxorubicin equivalent) intravenously on Day 1, every 21 days until  
evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Subjects will be 
randomly assigned to either dose of ALDOXORUBICIN.  G-CSF (Neupogen or Neulasta) should be 
administered as primary prophylaxis to all subjects according to the ASCO Guidelines (see  
Appendix E). 
Tumor response (complete response [CR], partial response [PR] and stable disease [SD]) will be 
monitored at Screening, then every 6 weeks ± 5 days using the RANO Working Group Criteria (see 
Appendix F), and treatment will continue every 21 days until tumor progression is observed, 
unacceptable toxicity occurs, or consent is withdrawn. Median PFS, PFS at 12 and 18 weeks, and  
6 months, SD rate at 12 weeks, and OS will be monitored as other primary objectives. Subjects will 
visit the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, 
a directed physical examination, laboratory evaluations (serum chemistry, complete blood count 
[CBC], and urinalysis), vital signs, weight measurements, Karnofsky Performance Status (see 
Appendix B), documentation of corticosteroid usage and ECGs will be performed.  Cardiac function 
will also be followed periodically using ECHOs. 


ALDOXORUBICIN-P2-GBM-01 Amendment 1                         
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose 
prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade 
glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into 
GBM. 
3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide 
with no other therapy prior to tumor recurrence.  
a. Radiographic progression by RANO Working Group Criteria (see Appendix F) will be 
confirmed by Imaging Endpoints, a central imaging vendor; or 
b. Confirmation by tumor biopsy if conducted within 4 weeks of Randomization. 
4. An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless 
cancer progression is proven by diagnostic tumor biopsy.  
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to Randomization. 
6. Capable of providing informed consent and complying with trial procedures. 
7. Karnofsky Performance Status (see Appendix B) ≥70. 
8. Life expectancy ≥8 weeks. 
9. Measurable tumor lesions according to RANO Working Group Criteria (see Appendix F). 
a. In the case that there is “non-measureable” disease due to a radical surgical resection prior 
to screening, the subject may still qualify if Inclusion #3(b) is met. 
10. 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.) 
11. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening 
Visit and be non-lactating. 
12. Geographic accessibility to the site, i.e. the ability to come to the study site for each scheduled 
appointment and evaluation. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to an anthracycline. 
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, 
radiation and temozolomide. 
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent. 
4. Palliative surgery and/or radiation treatment < 4 weeks prior to Randomization. 
5. Exposure to any investigational agent within 30 days of Randomization. 
6. 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. 
7. 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 <100,000/mm3, absolute lymphocyte count <1000/mm3, hematocrit 
level <27% for females or <30% for males, serum albumin ≤2.5 g/dL, prothrombin time 
(PT)/international normalized ratio (INR) ˃1.5×ULN or ˃3×ULN. 


ALDOXORUBICIN-P2-GBM-01 Amendment 1                         
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
8. Evidence of central nervous system (CNS) hemorrhage Common Terminology Criteria for 
Adverse Events (CTCAE) ≥ grade 2 on baseline magnetic resonance imaging (MRI). 
9. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (see Appendix D). 
10. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute 
arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix G). 
11. Baseline QTc >470 msec and/or previous history of QT prolongation. 
12. History or signs of active coronary artery disease with or without angina pectoris. 
13. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular 
ejection fraction (LVEF) <45% of predicted institutional normal value. 
14. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or  
anti-fungals. 
15. History of HIV infection. 
16. Major surgery, except diagnostic tumor biopsy, within 4 weeks prior to Randomization. 
17. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
18. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Up to 28 subjects will be enrolled (14 at each dose level) in 3-5 study centers in the US. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50:50 ethanol:water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total doses of either  
350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents). 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 OS 
 Objective tumor response (RANO Working Group Criteria [see Appendix F]) 
 PFS at 12 and 18 weeks and 6 months 
 SD rate at 12 weeks 
 Karnofsky Performance Status (see Appendix B) 
 Corticosteroid usage 
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 


ALDOXORUBICIN-P2-GBM-01 Amendment 1                         
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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.   
Efficacy:   
Tumor response by MRI will be monitored every 6 weeks until disease progression. For the 
estimation of PFS and OS a Kaplan-Meier analysis will be performed.  The percentage of subjects 
with CRs or PRs, or SD will be evaluated every 6 weeks.  
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, ECG results, ECHO, 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-GBM-01 Amendment 1 
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 46 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Every 6 Weeks 
± 5 Days from 
Cycle 1-Day 1 
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 Calculation2 
 
X 
X 
 
 
 
Vital Signs3 
X 
X 
X 
 
X 
 
Karnofsky Performance Status 
X 
X 
X 
 
X 
 
MRI scan / Tumor Assessments 
X4 
 
 
X8 
X8,13 
 
ECG 
X 
X15 
X15 
 
X13 
 
ECHO (with ejection fraction) 
X 
 
X11 
 
X11 
 
CBC w/differential & platelets5 
X 
X14 
X 
 
X 
 
Serum Chemistries5,6  
X 
X14 
X 
 
X 
 
Urinalysis7 
X 
 
 
 
X 
 
Serum/Urine Pregnancy Test 
X 
 
 
 
 
 
ALDOXORUBICIN Administration 
 
X 
X 
 
 
 
Concomitant Medications9 
X 
X 
X 
 
X 
 
Adverse Events10 
 
X 
X 
 
X 
 
Telephone Follow-Up 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (see Section 6 for details). 


ALDOXORUBICIN-P2-GBM-01 Amendment 1 
November 12, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 47 
1. To include concurrent baseline conditions (using NCI CTCAE, version 4.0 [published 28 
May 2009] [see Appendix C]), prior cancer therapy (including documentation of prior 
surgery, adjuvant or neoadjuvant chemotherapy, antibody therapy and radiotherapy). 
2. BSA only needs to be calculated if there has been a change >10% in body weight from 
Cycle 1-Day 1. 
3. Blood pressure, pulse, respiratory rate, and temperature. Vital signs will be monitored 
every 15 minutes starting immediately prior to ALDOXORUBICIN dosing and ending 
approximately 30 minutes after completion of infusion. 
4. MRI scan of brain with contrast to document disease status. If scan was taken within  
21 days prior to first dose, a new scan is not necessary. However, if a new scan is to be 
done, it should be performed within 7 days of starting chemotherapy.   
a. Historical MRI scans no older than 2 months prior to screening must be 
electronically submitted to Imaging Endpoints to confirm radiographic 
progression. 
b. All scans must be electronically submitted to Imaging Endpoints.  Please refer to 
your Imaging Manual for details. 
c. If a surgical resection was completed during the screening period and 
demonstrates disease progression, the MRI may show “non-measureable” 
disease and will be used to demonstrate disease progression only. 
5. During treatment, if any drug-related and/or clinically significant toxicity occurs, retest 
frequently until stable or resolving and in accordance with GCP.  Note: CBC with 
differential and platelet count must be performed weekly during each cycle. 
6. To include BUN, phosphorus, magnesium, LDH, creatinine, uric acid, total protein, 
albumin, calcium, glucose, total bilirubin, ALP, AST, ALT,  electrolytes (chloride, sodium, 
potassium, and bicarbonate), PT/INR (at screening only). 
7. Lab urinalysis to include protein, specific gravity, glucose, and blood. 
8. Tumor response must be monitored during treatment every 6 weeks ± 5 days from Cycle 
1-Day 1 regardless of dosing delays.  The final assessment to be done 3 weeks 
following final ALDOXORUBICIN administration. 
9. To include all medications taken within 30 days prior to study Randomization. 
10. Subject will be followed until resolution of any drug-related AE or SAE occurring 
during the study, including within 30 days of last administration of study medication, 
or when the subject begins alternative therapy; whichever is sooner.   
11. Cycle 4 and End of Treatment visit if later than Cycle 4.  Additional testing can be 
done if clinically indicated. 
12. Follow-up by telephone will be conducted in all subjects every 8 weeks to determine 
date of death. 
13. If not done within last 14 days. 
14. No need to repeat if performed within 21 days of Randomization. 
15. ECGs will be performed pre-dose and at 1 hour post-dose (the anticipated maximal 
concentration). 


 
CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate the Preliminary Efficacy and 
Safety of Aldoxorubicin in Subjects with 
Unresectable Glioblastoma Whose Tumors 
Have Progressed Following Prior Treatment 
with Surgery, Radiation and Temozolomide  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-GBM-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
119437 
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: 
August 9, 2013 
AMENDMENT 1: 
November 12, 2013 
AMENDMENT 2: 
February 4, 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-GBM-01 Amendment 2                         
February 4, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of 
Aldoxorubicin in Subjects with Unresectable Glioblastoma  Whose Tumors Have Progressed 
Following Prior Treatment with Surgery, Radiation and Temozolomide  
Primary Objectives: 
The primary objective of this study is to determine the preliminary efficacy of administration of 
ALDOXORUBICIN to subjects with unresectable glioblastoma (GBM) whose tumors have progressed 
following prior treatment with surgery, radiation and temozolomide, as measured by PFS according to 
the Response Assessment in Neuro-Oncology (RANO) Working Group Criteria (see Appendix F) and 
OS.  
Secondary Objectives: 
The secondary objectives of this study are 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, weight, and the change in performance status as measured by the 
Karnofsky Performance Scale. 
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 prodrug has demonstrated enhanced 
anti-tumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
Patients with unresectable GBM who have failed prior surgery, radiation and chemotherapy with 
temozolomide regimens and bevacizumab have an extremely poor prognosis with progression-free 
survival (PFS) of around 8 weeks and median overall survival (OS) of approximately 8-16 weeks, 
depending on whether salvage therapy is administered. Recently, we have demonstrated in an 
orthotopic xenograft model of GBM in mice that ALDOXORUBICIN significantly retards the growth of 
the tumor and doubles the survival of animals when compared to treatment with either saline or 
doxorubicin.  We have also shown that this molecule collects inside the tumor and not in normal brain 
parenchyma. Doxorubicin does not penetrate into either the tumor or the brain. Thus, 
ALDOXORUBICIN may be able to effectively treat patients with advanced GBM that have progressed 
after standard therapies. 


ALDOXORUBICIN-P2-GBM-01 Amendment 2                         
February 4, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or  
250 mg/m2 (185 mg/m2 doxorubicin equivalent) intravenously on Day 1, every 21 days until  
evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Subjects will be 
randomly assigned to either dose of ALDOXORUBICIN.  G-CSF (Neupogen or Neulasta) should be 
administered as primary prophylaxis to all subjects according to the ASCO Guidelines (see  
Appendix E). 
Tumor response (complete response [CR], partial response [PR] and stable disease [SD]) will be 
monitored at Screening, then every 6 weeks ± 5 days using the RANO Working Group Criteria (see 
Appendix F), and treatment will continue every 21 days until tumor progression is observed, 
unacceptable toxicity occurs, or consent is withdrawn. Median PFS, PFS at 12 and 18 weeks, and  
6 months, SD rate at 12 weeks, and OS will be monitored as other primary objectives. Subjects will 
visit the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, 
a directed physical examination, laboratory evaluations (serum chemistry, complete blood count 
[CBC], and urinalysis), vital signs, weight measurements, Karnofsky Performance Status (see 
Appendix B), documentation of corticosteroid usage and ECGs will be performed.  Cardiac function 
will also be followed periodically using ECHOs. 


ALDOXORUBICIN-P2-GBM-01 Amendment 2                         
February 4, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose 
prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade 
glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into 
GBM. 
3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide 
with no other therapy prior to tumor recurrence.  
a. Radiographic progression by RANO Working Group Criteria (see Appendix F) will be 
confirmed by Imaging Endpoints, a central imaging vendor; or 
b. Confirmation by tumor biopsy if conducted within 4 weeks of Randomization. 
4. An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless 
cancer progression is proven by diagnostic tumor biopsy.  If temozolomide is being used in a 
maintenance phase, there must be a 28-day washout period prior to Randomization. 
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to Randomization. 
6. Capable of providing informed consent and complying with trial procedures. 
7. Karnofsky Performance Status (see Appendix B) ≥70. 
8. Life expectancy ≥8 weeks. 
9. Measurable tumor lesions according to RANO Working Group Criteria (see Appendix F). 
a. In the case that there is “non-measureable” disease due to a radical surgical resection prior 
to screening, the subject may still qualify if Inclusion #3(b) is met. 
10. 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.) 
11. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening 
Visit and be non-lactating. 
12. Geographic accessibility to the site, i.e. the ability to come to the study site for each scheduled 
appointment and evaluation. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to an anthracycline. 
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, 
radiation and temozolomide. 
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent. 
4. Palliative surgery and/or radiation treatment < 4 weeks prior to Randomization. 
5. Exposure to any investigational agent within 30 days of Randomization. 
6. 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. 
7. 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 <100,000/mm3, absolute lymphocyte count <1000/mm3,  
hematocrit level <27% for females or <30% for males, serum albumin ≤2.5 g/dL, prothrombin time 
(PT)/ international normalized ratio (INR) ˃1.5×ULN or ˃3×ULN on anticoagulant with no evidence of 
active bleeding.  


ALDOXORUBICIN-P2-GBM-01 Amendment 2                         
February 4, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
8. Evidence of central nervous system (CNS) hemorrhage Common Terminology Criteria for 
Adverse Events (CTCAE) ≥ grade 2 on baseline magnetic resonance imaging (MRI). 
9. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (see Appendix D). 
10. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute 
arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix G). 
11. Baseline QTc >470 msec and/or previous history of QT prolongation. 
12. History or signs of active coronary artery disease with or without angina pectoris. 
13. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular 
ejection fraction (LVEF) <45% of predicted institutional normal value. 
14. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or  
anti-fungals. 
15. History of HIV infection. 
16. Major surgery, except diagnostic tumor biopsy, within 4 weeks prior to Randomization. 
17. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
18. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Up to 28 subjects will be enrolled (14 at each dose level) in 3-5 study centers in the US. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50:50 ethanol:water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total doses of either  
350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents). 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 OS 
 Objective tumor response (RANO Working Group Criteria [see Appendix F]) 
 PFS at 12 and 18 weeks and 6 months 
 SD rate at 12 weeks 
 Karnofsky Performance Status (see Appendix B) 
 Corticosteroid usage 
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 


ALDOXORUBICIN-P2-GBM-01 Amendment 2                         
February 4, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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.   
Efficacy:   
Tumor response by MRI will be monitored every 6 weeks until disease progression. For the 
estimation of PFS and OS a Kaplan-Meier analysis will be performed.  The percentage of subjects 
with CRs or PRs, or SD will be evaluated every 6 weeks.  
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, ECG results, ECHO, 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-GBM-01 Amendment 2 
February 4, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 46 
APPENDIX A: Schedule of Treatment and Evaluations 
Screening 
-21 Days
Cycle 1 All Other 
Cycles 
Every 6 Weeks 
± 5 Days from 
Cycle 1-Day 1 
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 Calculation2
X 
X 
Vital Signs3
X 
X 
X 
X 
Karnofsky Performance Status 
X 
X 
X 
X 
MRI scan / Tumor Assessments 
X4
X8
X8,13
ECG 
X 
X15
X15
X13
ECHO (with ejection fraction) 
X 
X11
X11
CBC w/differential & platelets5
X 
X14
X 
X 
Serum Chemistries5,6
X 
X14
X 
X 
Urinalysis7
X 
X 
Serum/Urine Pregnancy Test 
X 
ALDOXORUBICIN Administration 
X 
X 
Concomitant Medications9 
X 
X 
X 
X 
Adverse Events10 
X 
X 
X 
Telephone Follow-Up
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (see Section 6 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate the Preliminary Efficacy and 
Safety of Aldoxorubicin in Subjects with 
Unresectable Glioblastoma Whose Tumors 
Have Progressed Following Prior Treatment 
with Surgery, Radiation and Temozolomide  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-GBM-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
119437 
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: 
August 9, 2013 
AMENDMENT 1: 
November 12, 2013 
AMENDMENT 2: 
February 4, 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-GBM-01 Amendment 3                         
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of 
Aldoxorubicin in Subjects with Unresectable Glioblastoma  Whose Tumors Have Progressed 
Following Prior Treatment with Surgery, Radiation and Temozolomide  
Primary Objectives: 
The primary objective of this study is to determine the preliminary efficacy of administration of 
ALDOXORUBICIN to subjects with unresectable glioblastoma (GBM) whose tumors have progressed 
following prior treatment with surgery, radiation and temozolomide, as measured by PFS according to 
the Response Assessment in Neuro-Oncology (RANO) Working Group Criteria (see Appendix F) and 
OS.  
Secondary Objectives: 
The secondary objectives of this study are 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, weight, and the change in performance status as measured by the 
Karnofsky Performance Scale. 
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 prodrug has demonstrated enhanced 
anti-tumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
Patients with unresectable GBM who have failed prior surgery, radiation and chemotherapy with 
temozolomide regimens and bevacizumab have an extremely poor prognosis with progression-free 
survival (PFS) of around 8 weeks and median overall survival (OS) of approximately 8-16 weeks, 
depending on whether salvage therapy is administered. Recently, we have demonstrated in an 
orthotopic xenograft model of GBM in mice that ALDOXORUBICIN significantly retards the growth of 
the tumor and doubles the survival of animals when compared to treatment with either saline or 
doxorubicin.  We have also shown that this molecule collects inside the tumor and not in normal brain 
parenchyma. Doxorubicin does not penetrate into either the tumor or the brain. Thus, 
ALDOXORUBICIN may be able to effectively treat patients with advanced GBM that have progressed 
after standard therapies. 


ALDOXORUBICIN-P2-GBM-01 Amendment 3                         
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or  
250 mg/m2 (185 mg/m2 doxorubicin equivalent) intravenously on Day 1, every 21 days until  
evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Subjects will be 
randomly assigned to either dose of ALDOXORUBICIN.  G-CSF (Neupogen or Neulasta) should be 
administered as primary prophylaxis to all subjects according to the ASCO Guidelines (see  
Appendix E). 
Tumor response (complete response [CR], partial response [PR] and stable disease [SD]) will be 
monitored at Screening, then every 6 weeks ± 5 days using the RANO Working Group Criteria (see 
Appendix F), and treatment will continue every 21 days until tumor progression is observed, 
unacceptable toxicity occurs, or consent is withdrawn. Median PFS, PFS at 12 and 18 weeks, and  
6 months, SD rate at 12 weeks, and OS will be monitored as other primary objectives. Subjects will 
visit the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, 
a directed physical examination, laboratory evaluations (serum chemistry, complete blood count 
[CBC], and urinalysis), vital signs, weight measurements, Karnofsky Performance Status (see 
Appendix B), documentation of corticosteroid usage and ECGs will be performed.  Cardiac function 
will also be followed periodically using ECHOs. 


ALDOXORUBICIN-P2-GBM-01 Amendment 3                         
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose 
prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade 
glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into 
GBM. 
3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide 
with no other therapy prior to tumor recurrence.  
a. Radiographic progression by RANO Working Group Criteria (see Appendix F) will be 
confirmed by Imaging Endpoints, a central imaging vendor; or 
b. Confirmation by tumor biopsy if conducted within 4 weeks of Randomization. 
4. An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless 
cancer progression is proven by diagnostic tumor biopsy.  If temozolomide is being used in a 
maintenance phase, there must be a 28-day washout period prior to Randomization. 
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to Randomization. 
6. Capable of providing informed consent and complying with trial procedures. 
7. Karnofsky Performance Status (see Appendix B) ≥70. 
8. Life expectancy ≥8 weeks. 
9. Measurable tumor lesions according to RANO Working Group Criteria (see Appendix F). 
a. In the case that there is “non-measureable” disease due to a radical surgical resection prior 
to screening, the subject may still qualify if Inclusion #3(b) is met. 
10. 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.) 
11. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening 
Visit and be non-lactating. 
12. Geographic accessibility to the site, i.e. the ability to come to the study site for each scheduled 
appointment and evaluation. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to an anthracycline. 
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, 
radiation and temozolomide. 
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent. 
4. Palliative surgery and/or radiation treatment < 4 weeks prior to Randomization. 
5. Exposure to any investigational agent within 30 days of Randomization. 
6. 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. 
7. 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 <100,000/mm3, absolute lymphocyte count <1000/mm3,  
hematocrit level <27% for females or <30% for males, serum albumin ≤2.5 g/dL, prothrombin time 
(PT)/ international normalized ratio (INR) ˃1.5×ULN or ˃3×ULN on anticoagulant with no evidence of 
active bleeding.  


ALDOXORUBICIN-P2-GBM-01 Amendment 3                         
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
8. Evidence of central nervous system (CNS) hemorrhage Common Terminology Criteria for 
Adverse Events (CTCAE) ≥ grade 2 on baseline magnetic resonance imaging (MRI). 
9. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (see Appendix D). 
10. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute 
arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix G). 
11. Baseline QTc >470 msec and/or previous history of QT prolongation. 
12. History or signs of active coronary artery disease with or without angina pectoris. 
13. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular 
ejection fraction (LVEF) <45% of predicted institutional normal value. 
14. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or  
anti-fungals. 
15. History of HIV infection. 
16. Major surgery, except diagnostic tumor biopsy, within 4 weeks prior to Randomization. 
17. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
18. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Up to 28 subjects will be enrolled (14 at each dose level) in 3-5 study centers in the US. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50:50 ethanol:water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total doses of either  
350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents). 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 OS 
 Objective tumor response (RANO Working Group Criteria [see Appendix F]) 
 PFS at 12 and 18 weeks and 6 months 
 SD rate at 12 weeks 
 Karnofsky Performance Status (see Appendix B) 
 Corticosteroid usage 
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 


ALDOXORUBICIN-P2-GBM-01 Amendment 3                         
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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.   
Efficacy:   
Tumor response by MRI will be monitored every 6 weeks until disease progression. For the 
estimation of PFS and OS a Kaplan-Meier analysis will be performed.  The percentage of subjects 
with CRs or PRs, or SD will be evaluated every 6 weeks.  
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, ECG results, ECHO, 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-GBM-01 Amendment 3 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 46 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Every 6 Weeks 
± 5 Days from 
Cycle 1-Day 1 
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 Calculation2 
 
X 
X 
 
 
 
Vital Signs3 
X 
X 
X 
 
X 
 
Karnofsky Performance Status 
X 
X 
X 
 
X 
 
MRI scan / Tumor Assessments 
X4 
 
 
X8 
X8,13 
 
ECG 
X 
X15 
X15 
 
X13 
 
ECHO (with ejection fraction) 
X 
 
X11 
 
X11 
 
CBC w/differential & platelets5 
X 
X14 
X 
 
X 
 
Serum Chemistries5,6  
X 
X14 
X 
 
X 
 
Urinalysis7 
X 
 
 
 
X 
 
Serum/Urine Pregnancy Test 
X 
 
 
 
 
 
ALDOXORUBICIN Administration 
 
X 
X 
 
 
 
Concomitant Medications9 
X 
X 
X 
 
X 
 
Adverse Events10 
 
X 
X 
 
X 
 
Telephone Follow-Up 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (see Section 6 for details). 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate the Preliminary Efficacy and 
Safety of Aldoxorubicin in Subjects with 
Unresectable Glioblastoma Whose Tumors 
Have Progressed Following Prior Treatment 
with Surgery, Radiation and Temozolomide  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-GBM-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
119437 
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: 
August 9, 2013 
AMENDMENT 1: 
November 12, 2013 
AMENDMENT 2: 
February 4, 2014 
AMENDMENT 3: 
September 10, 2014 
AMENDMENT 4: 
January 14, 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-GBM-01 A4                         
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of 
Aldoxorubicin in Subjects with Unresectable Glioblastoma  Whose Tumors Have Progressed 
Following Prior Treatment with Surgery, Radiation and Temozolomide  
Primary Objectives: 
The primary objective of this study is to determine the preliminary efficacy of administration of 
ALDOXORUBICIN to subjects with unresectable glioblastoma (GBM) whose tumors have progressed 
following prior treatment with surgery, radiation and temozolomide, as measured by PFS according to 
the Response Assessment in Neuro-Oncology (RANO) Working Group Criteria (see Appendix F) and 
OS.  
Secondary Objectives: 
The secondary objectives of this study are 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, weight, and the change in performance status as measured by the 
Karnofsky Performance Scale. 
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 prodrug has demonstrated enhanced 
anti-tumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
Patients with unresectable GBM who have failed prior surgery, radiation and chemotherapy with 
temozolomide regimens and bevacizumab have an extremely poor prognosis with progression-free 
survival (PFS) of around 8 weeks and median overall survival (OS) of approximately 8-16 weeks, 
depending on whether salvage therapy is administered. Recently, we have demonstrated in an 
orthotopic xenograft model of GBM in mice that ALDOXORUBICIN significantly retards the growth of 
the tumor and doubles the survival of animals when compared to treatment with either saline or 
doxorubicin.  We have also shown that this molecule collects inside the tumor and not in normal brain 
parenchyma. Doxorubicin does not penetrate into either the tumor or the brain. Thus, 
ALDOXORUBICIN may be able to effectively treat patients with advanced GBM that have progressed 
after standard therapies. 


ALDOXORUBICIN-P2-GBM-01 A4                         
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or  
250 mg/m2 (185 mg/m2 doxorubicin equivalent) intravenously on Day 1, every 21 days until  
evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Subjects will be 
randomly assigned to either dose of ALDOXORUBICIN.  G-CSF (Neupogen or Neulasta) should be 
administered as primary prophylaxis to all subjects according to the ASCO Guidelines (see  
Appendix E).  Note:  ALDOXORUBICIN, at higher doses, has been associated with >20% 
incidence of grade 3 or 4 neutropenia. Therefore, the administration of G-CSF should occur 
even during Cycle 1 for subjects receiving the 350 mg/m2 dose of ALDOXORUBICIN. 
Tumor response (complete response [CR], partial response [PR] and stable disease [SD]) will be 
monitored at Screening, then every 6 weeks (±5 days) using the RANO Working Group Criteria (see 
Appendix F), and treatment will continue every 21 days until tumor progression is observed, 
unacceptable toxicity occurs, or consent is withdrawn. Median PFS, PFS at 12 and 18 weeks, and  
6 months, SD rate at 12 weeks, and OS will be monitored as other primary objectives. Subjects will 
visit the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, 
a directed physical examination, laboratory evaluations (serum chemistry and complete blood count 
[CBC]), vital signs, weight measurements, Karnofsky Performance Status (see Appendix B), 
documentation of corticosteroid usage and ECGs will be performed.  All subjects will have blood 
drawn for serum electrolytes to evaluate the anion gap prior to each drug administration. Cardiac 
function will also be followed periodically using ECHOs. 


ALDOXORUBICIN-P2-GBM-01 A4                         
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose 
prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade 
glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into 
GBM. 
3. Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide 
with no other therapy prior to tumor recurrence.  
a. Radiographic progression by RANO Working Group Criteria (see Appendix F) will be 
confirmed by Imaging Endpoints, a central imaging vendor; or 
b. Confirmation by tumor biopsy if conducted within 4 weeks of Randomization. 
4. An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless 
cancer progression is proven by diagnostic tumor biopsy.  If temozolomide is being used in a 
maintenance phase, there must be a 28-day washout period prior to Randomization. 
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to Randomization. 
6. Capable of providing informed consent and complying with trial procedures. 
7. Karnofsky Performance Status (see Appendix B) ≥70. 
8. Life expectancy ≥8 weeks. 
9. Measurable tumor lesions according to RANO Working Group Criteria (see Appendix F). 
a. In the case that there is “non-measureable” disease due to a radical surgical resection prior 
to screening, the subject may still qualify if Inclusion #3(b) is met. 
10. 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.) 
11. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening 
Visit and be non-lactating. 
12. Geographic accessibility to the site, i.e. the ability to come to the study site for each scheduled 
appointment and evaluation. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to an anthracycline. 
2. Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, 
radiation and temozolomide. 
3. Prior treatment with bevacizumab or an experimental anti-angiogenic agent. 
4. Palliative surgery and/or radiation treatment < 4 weeks prior to Randomization. 
5. Exposure to any investigational agent within 30 days of Randomization. 
6. 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. 
7. 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 <100,000/mm3, absolute lymphocyte count <1000/mm3,  
hematocrit level <27% for females or <30% for males, serum albumin ≤2.5 g/dL, prothrombin time 
(PT)/ international normalized ratio (INR) ˃1.5×ULN or ˃3×ULN on anticoagulant with no evidence of 
active bleeding.  


ALDOXORUBICIN-P2-GBM-01 A4                         
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
8. Anion gap > 16 meq/L or arterial blood pH < 7.30. 
9. Evidence of central nervous system (CNS) hemorrhage Common Terminology Criteria for 
Adverse Events (CTCAE) ≥ grade 2 on baseline magnetic resonance imaging (MRI). 
10. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (see Appendix D). 
11. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute 
arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix G). 
12. Baseline QTc >470 msec and/or previous history of QT prolongation. 
13. History or signs of active coronary artery disease with or without angina pectoris. 
14. Serious myocardial dysfunction defined as ultrasound-determined absolute left ventricular 
ejection fraction (LVEF) <45% of predicted institutional normal value. 
15. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or  
anti-fungals. 
16. History of HIV infection. 
17. Major surgery, except diagnostic tumor biopsy, within 4 weeks prior to Randomization. 
18. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
19. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Up to 28 subjects will be enrolled (14 at each dose level) in 3-5 study centers in the US. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50:50 ethanol:water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total doses of either  
350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents). 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
• PFS 
• OS 
• Objective tumor response (RANO Working Group Criteria [see Appendix F]) 
• PFS at 12 and 18 weeks and 6 months 
• SD rate at 12 weeks 
• Pseudo progression events on DSC-MRI in subjects who undergo additional MRI sequence 
evaluation 
• Karnofsky Performance Status (see Appendix B) 
• Corticosteroid usage 


ALDOXORUBICIN-P2-GBM-01 A4                         
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
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 
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.   
Efficacy:   
Tumor response by MRI will be monitored every 6 weeks (±5 days) until disease progression. For the 
estimation of PFS and OS a Kaplan-Meier analysis will be performed.  The percentage of subjects 
with CRs or PRs, or SD will be evaluated every 6 weeks.  
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, ECG results, ECHO, 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-GBM-01 A4 
January 14, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 50 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All Other 
Cycles 
Every 6 Weeks
± 5 Days from 
Cycle 1-Day 1
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 Calculation2 
 
X 
X 
 
 
 
Vital Signs3 
X 
X 
X 
 
X 
 
Karnofsky Performance Status 
X 
X 
X 
 
X 
 
MRI scan / Tumor Assessments 
X4 
 
 
X8 
X8,13 
 
ECG 
X 
X15 
X15 
 
X13 
 
ECHO (with ejection fraction) 
X 
 
X11 
 
X11 
 
CBC w/differential & platelets5 
X 
X14 
X 
 
X 
 
Serum Chemistries5,6  
X* 
X14 
X 
 
X 
 
Urinalysis7 
X 
 
 
 
X 
 
Serum/Urine Pregnancy Test 
X 
 
 
 
 
 
ALDOXORUBICIN Administration 
 
X 
X 
 
 
 
Concomitant Medications9 
X 
X 
X 
 
X 
 
Adverse Events10 
 
X 
X 
 
X 
 
Telephone Follow-Up 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hours of each specified time parameter, except Cycle 1 (see Section 6 for details). 
*Arterial blood gas test, if needed, to confirm acid levels. 


CLINICAL PROTOCOL 
TITLE: 
An Open-Label Pilot Phase 2 Study to 
Investigate the Preliminary Efficacy and 
Safety of Aldoxorubicin in Subjects with 
Unresectable Glioblastoma Multiforme Whose 
Tumors Have Progressed Following Prior 
Treatment with Surgery, Radiation and 
Temozolomide  
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-GBM-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
TBD 
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: 
August 9, 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-GBM-01                          
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
SYNOPSIS 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Title of the Protocol:  
An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of 
Aldoxorubicin in Subjects with Unresectable Glioblastoma Multiforme Whose Tumors Have 
Progressed Following Prior Treatment with Surgery, Radiation and Temozolomide  
Primary Objectives: 
The primary objective of this study is to determine the preliminary efficacy of administration of 
ALDOXORUBICIN to subjects with unresectable glioblastoma multiforme (GBM) whose tumors have 
progressed following prior treatment with surgery, radiation and temozolomide.  
Secondary Objectives: 
The secondary objectives of this study are 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, and the change in performance status as measured by 
the Karnofsky Performance Scale. 
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 prodrug has demonstrated enhanced 
anti-tumor activity with reduced toxicity in several murine models when compared with free 
doxorubicin. 
Patients with unresectable GBM who have failed prior surgery, radiation and chemotherapy with 
temozolomide regimens and bevacizumab have an extremely poor prognosis with progression-free 
survival (PFS) of around 8 weeks and median overall survival (OS) of approximately 8-16 weeks, 
depending on whether salvage therapy is administered. Recently, we have demonstrated in an 
orthotopic xenograft model of GBM in mice that ALDOXORUBICIN significantly retards the growth of 
the tumor and doubles the survival of animals when compared to treatment with either saline or 
doxorubicin.  We have also shown that this molecule collects inside the tumor and not in normal brain 
parenchyma. Doxorubicin does not penetrate into either the tumor or the brain. Thus,   
ALDOXORUBICIN may be able to effectively treat patients with advanced GBM that have progressed 
after standard therapies. 


ALDOXORUBICIN-P2-GBM-01                          
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
Study Design and Methodology: 
This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of 
ALDOXORUBICIN administered at either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 
mg/m2 (185 mg/m2 doxorubicin equivalent) intravenously on Day 1, every 21 days until evidence of 
tumor progression, unacceptable toxicity or withdrawal of consent. Subjects will be randomly 
assigned to either dose of ALDOXORUBICIN.  G-CSF (Neupogen or Neulasta) should be 
administered prophylactically according to the ASCO Guidelines (see Appendix E). 
Tumor response (complete, partial response [PR] and stable disease [SD]) will be monitored at 
Screening, then every 6 weeks using the Response Assessment in Neuro-Oncology (RANO) Working 
Group Criteria (see Appendix F), and treatment will continue every 21 days until tumor progression is 
observed, unacceptable toxicity occurs, or consent is withdrawn. Median PFS, PFS at 12 and 18 
weeks, SD rate at 12 weeks, and OS will be monitored as other primary objectives. Subjects will visit 
the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, a 
directed physical examination, laboratory evaluations (serum chemistry, complete blood count [CBC], 
and urinalysis), vital signs, weight measurements, Karnofsky Performance Status (see Appendix B), 
corticosteroid usage and ECGs will be performed.  Cardiac function will also be followed periodically 
using ECHOs. 


ALDOXORUBICIN-P2-GBM-01                          
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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. Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease 
whose prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-
grade glioma or anaplastic glioma are eligible if histological assessment demonstrates 
transformation into GBM. 
3. Cancer progression after treatment with the following: surgery, radiation therapy and 
temozolomide as first line treatment.  
4. An interval of at least 4 weeks after last dose of radiation and temozolomide is required.  
5. Stable or decreasing dose of corticosteroids for at least 7 days prior to enrollment. 
6. Capable of providing informed consent and complying with trial procedures. 
7. Karnofsky Performance Status (see Appendix B) ≥70. 
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 
9. Life expectancy ≥8 weeks. 
10. Measurable tumor lesions according to RANO Working Group Criteria (see Appendix F). 
11. 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.) 
12. Women of child bearing potential must have a negative serum or urine pregnancy test at the 
Screening Visit and be non-lactating. 
13. Geographic accessibility to the site. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to an anthracycline. 
2. Prior treatment with bevacizumab or an experimental anti-angiogenic agent. 
3. Palliative surgery and/or radiation treatment < 4 weeks prior to Randomization. 
4. Exposure to any investigational agent within 30 days of Randomization. 
5. 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. 
6. 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 <100,000/mm3, absolute lymphocyte count <1000/mm3, 
hematocrit level <27% for females or <30% for males, serum albumin ≤2.5 g/dL. 
7. Evidence of central nervous system (CNS) hemorrhage Common Terminology Criteria for 
Adverse Events (CTCAE) ≥ grade 2 on baseline magnetic resonance imaging (MRI). 
8. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (see Appendix D). 
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. 


ALDOXORUBICIN-P2-GBM-01                          
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-01 
 
Phase of Development: 2 
 
12. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or  
anti-fungals. 
13. History of HIV infection. 
14. Major surgery within 4 weeks prior to Randomization. 
15. Any condition that might interfere with the subject’s participation in the study or in the evaluation 
of the study results. 
16. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Up to 28 subjects will be enrolled (14 at each dose level) in 3-5 study centers in the US. 
Test Product, Dose and Mode of Administration: 
Lyophilized powder in vials that contain 200 mg of ALDOXORUBICIN reconstituted by adding a 
sterile solution of 50/50 ethanol:water, administration completed within 2 hours (of being 
reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total doses of either 350 
mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents). 
Reference Therapy, Dose and Mode of Administration: 
None 
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 OS 
 Objective tumor response (RANO Working Group Criteria [see Appendix F]) 
 PFS at 12 and 18 weeks 
 SD rate at 12 weeks 
 Karnofsky Performance Status (see Appendix B) 
 Corticosteroid usage 
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 


ALDOXORUBICIN-P2-GBM-01                          
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-GBM-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.   
Efficacy:   
Tumor response by MRI will be monitored every 6 weeks until disease progression. For the 
estimation of PFS and OS a Kaplan-Meier analysis will be performed.  The percentage of subjects 
with complete or PRs, or SD will be evaluated every 6 weeks.  
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, ECG results, ECHO, 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-GBM-01 
August 9, 2013 
 
CytRx Corporation 
CONFIDENTIAL 
Page 45 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-21 Days 
Cycle 1 All other 
cycles 
Every other 
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 calculation2 
 
X 
X 
 
 
 
Vital signs3 
X 
X 
X 
 
X 
 
Karnofsky  Performance Status 
X 
X 
X 
 
X 
 
MRI scan / tumor assesments 
X4 
 
 
X8 
X13 
 
ECG 
X 
X 
X 
 
X 
 
ECHO (with ejection fraction) 
X 
 
X11 
 
X11 
 
CBC w/differential & plts5 
X 
X 
X 
 
X 
 
Serum chemistries5,6  
X 
X14 
X 
 
X 
 
Urinalysis7 
X 
 
 
 
X 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
ALDOXORUBICIN administration 
 
X 
X 
 
 
 
Concomitant medications9 
X 
X 
X 
 
X 
 
Adverse events10 
 
X 
X 
 
X 
 
Telephone follow-up 
 
 
 
 
 
X 
NOTE: All assessments must be performed within 72 hour of each specified time parameter, except Cycle 1 (see Section 6 for details).