Clinical trial NCT02200757
Conditions: Metastatic Small Cell Lung Cancer
Sponsor: ImmunityBio, Inc.
Start date: 2015-04-20; Completion date: 2017-05-15
Enrollment: 135 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of aldoxorubicin compared to topotecan in subjects with metastatic small cell lung cancer.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Aldoxorubicin intervention 2: Topotecan
Intervention descriptions: intervention 1: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs. intervention 2: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL PROTOCOL 
TITLE: 
A Multicenter, Randomized, Open-Label Phase 2b Study 
to Investigate the Efficacy and Safety of Aldoxorubicin 
Compared to Topotecan in Subjects with Metastatic 
Small Cell Lung Cancer Who Either Relapsed or Were 
Refractory to Prior Chemotherapy 
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-SCLC-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
75,478 
EUDRACT NUMBER: 
2014-002189-64 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd., Suite 650 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY FAX: 
United States: 1-800-361-9714 
Czech Republic: 800-66-77-88 
Italy: 02-4074-6066 (Milan) 
Spain: 900-804-637 
Hungary: 06-80-10-2323 or 00-800-8000-0723 
South Korea:  use email 
SAFETY EMAIL: 
safetydesk@psi-cro.com 
DATE OF PROTOCOL: 
June 20, 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-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
Protocol Synopsis 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Title of the Protocol:  
A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of 
Aldoxorubicin Compared to Topotecan in Subjects with Metastatic Small Cell Lung Cancer Who 
Either Relapsed or Were Refractory to Prior Chemotherapy 
Primary Objective: 
The primary objective of this study is to determine the efficacy of administration of aldoxorubicin 
compared to topotecan in subjects with metastatic small cell lung cancer (SCLC) who have relapsed 
or were refractory to prior chemotherapy, as measured by progression-free survival (PFS). 
Secondary Objectives: 
The secondary objectives of this study are to evaluate the efficacy of aldoxorubicin as measured by 
overall survival (OS), safety of aldoxorubicin compared to topotecan 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, as well as disease control rate and tumor response. 
Study Rationale and Significance: 
Aldoxorubicin (INNO-206; DOXO-EMCH) 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 antitumor activity with reduced toxicity in several murine models when 
compared with free doxorubicin. 
Patients with metastatic SCLC who have failed prior chemotherapies have a poor prognosis with 
response rates of <10-25%, PFS of around  2-4 months and median OS of approximately 6-10 
months, depending on the initial duration of response to first line treatment.  Several chemotherapy 
regimens have been explored as palliative therapy for subjects with these patients and include such 
agents as topotecan (only approved agent in the US), topotecan plus platinum, cyclophosphamide + 
doxorubicin + vincristine (CAV) and amirubicin (not approved in US). However, these regimens can 
be quite toxic and have not significantly impacted either PFS or OS in these individuals.  
Aldoxorubicin may improve upon the activity of these drugs without an increase in toxicity as has 
been demonstrated in animal studies. 


ALDOXORUBICIN-P2-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Study Design and Methodology: 
This is a phase 2b open-label study evaluating the efficacy and safety of aldoxorubicin administered 
at 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21 days compared to 
topotecan administered either IV at doses of 1.5 mg/m2/day for 5 consecutive days starting on Day 1, 
and repeated every 21 days, or 4 mg/m2 administered as a 30 min IV infusion on Days 1, 8 and 15 
every 28 days. Subjects will be randomized 1:1 to receive either aldoxorubicin or topotecan. 
Pretreatment with granulocyte colony-stimulating factor (G-CSF) is permitted according to ASCO 
Guidelines (Appendix E).[31]  
Subjects will visit the study site on Day 1 of each cycle. Safety monitoring, including AEs, a directed 
physical examination, laboratory evaluations (serum chemistry, complete blood count [CBC], and 
urinalysis), vital signs, weight measurements, Eastern Cooperative Group performance status (ECOG 
PS) and ECGs will be performed on Day 1 of each cycle (for all subjects).  They will have CBCs and 
serum chemistries on Day 15 and Day 21 (if Day 21 does not correspond to Day 1 of the next cycle, 
±3 days) of each cycle as well. Cardiac function will also be followed periodically (per schedule of 
evaluations) with ECHO for subjects receiving aldoxorubicin. Treatment will continue until tumor 
progression is observed, subject asks to withdraw, or unacceptable toxicity occurs.  
Tumor response will be monitored at baseline, every 6 weeks from Cycle 1-Day 1 through week 33, 
and then every 12 weeks until disease progression using the Response Evaluation Criteria in Solid 
Tumors (RECIST) 1.1 criteria.[22] Overall survival, PFS, and PFS at 4 and 6 months will be evaluated. 
Objective response rate (ORR; complete response [CR] and partial response [PR]), disease control 
rate (ORR plus stable disease [SD] at 4 months) and quality of life (ECOG PS) will be assessed.  
 


ALDOXORUBICIN-P2-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
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 male or female. 
2. Histological confirmation of SCLC. 
3. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable 
by either surgery or radiation. 
4. Capable of providing informed consent and complying with trial procedures. 
5. ECOG PS 0-2. 
6. Life expectancy >8 weeks. 
7. Measurable tumor lesions according to RECIST 1.1 criteria.[22] 
8. 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.) 
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective 
contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual 
period of the female partner during the study treatment and for 6 months after the final dose of 
study treatment. 
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the 
Screening Visit and be non-lactating. 
11. Accessibility to the site that ensures the subject will be able to keep all study-related 
appointments. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin. 
2. Prior treatment with topotecan.   
3. Palliative surgery and/or radiation treatment < 21 days prior to date of randomization. 
4. Exposure to any investigational agent within 30 days of date of randomization. 
5. Exposure to any systemic chemotherapy within 21 days of date of randomization. 
6. Active (symptomatic) central nervous system (CNS) metastasis.  
7. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell 
carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless 
documented free of cancer for ≥3 years. 
8. Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine 
aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin 
>2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, 
hemoglobin <9 g/dL, albumin <2 gm/dL. 
9. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (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 F). 


ALDOXORUBICIN-P2-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
11. Baseline QTc >470 msec measured by Fridericia’s formula (QTcF) and/or previous history of QT 
prolongation while taking other medications. Concomitant use of medications associated with a 
high incidence of QT prolongation is not allowed. 
12. History or signs of active coronary artery disease with angina pectoris within the last 6 months. 
13. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) below the institution’s lower limit of predicted normal. 
14. Known history of HIV infection. 
15. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-
fungals. 
16. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, 
saquinavir. 
17. Major surgery within 30 days prior to date of randomization. 
18. Substance abuse or 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: 
Approximately 132 subjects with metastatic SCLC who have either not responded to or have 
progressed after treatment with no more than 1 prior systemic regimens will be randomized 1:1 
(aldoxorubicin:topotecan) at approximately 30 study centers in the US, Europe, and Asia. The 
randomization will be stratified according to their initial PS (ECOG PS 0-1 vs 2), and whether they 
had relapsed < or > 90 days after completing their initial therapy. 
Test Product and Mode of Administration: 
Aldoxorubicin: Lyophilized powder in vials that contain 200 mg of aldoxorubicin reconstituted by 
adding a solution of 50% ethanol: 50% sterile water, administration completed within 2 hours (of 
being reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total dose of 
230 mg/m2 (170 mg/m2 doxorubicin equivalent). 
Topotecan:  
Topotecan for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder 
available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of 
topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is 
intended for administration by intravenous infusion (IVI). Each topotecan 4-mg vial is reconstituted 
with 4 mL Sterile Water for Injection. Then the appropriate volume of the reconstituted solution is 
diluted in either 0.9% Sodium Chloride IVI or 5% Dextrose IVI prior to administration. Because the 
lyophilized dosage form contains no antibacterial preservative, the reconstituted product should be 
used immediately.  
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 OS 
 Objective tumor response (RECIST 1.1 criteria).[22] 
 Disease control rate (ORR + SD at 4 months). 
 Investigator assessment as measured by ECOG PS. 


ALDOXORUBICIN-P2-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Safety: 
The following safety variables will be assessed over the duration 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 will be evaluated for 
efficacy. All subjects who receive at least 1 dose of study medication will be evaluated for safety.  
Efficacy:   
The primary analysis of PFS will be carried out approximately 6 months following the completion of 
enrollment of 132 subjects. Survival distributions will be estimated using the Kaplan-Meier method 
and the 2 groups will be compared using a two-sided log rank test at the α=0.05 level of significance. 
The final analysis of OS will be completed when 110 OS events have occurred. Survival distributions 
will be estimated using the Kaplan-Meier method and the 2 groups will be compared using a two-
sided log rank test. 
Tumor response will be monitored at baseline, every 6 weeks from Cycle 1-Day 1 through week 33, 
and then every 12 weeks until disease progression. The percentage of subjects with CR or PR, or SD 
will be evaluated and the disease control rate (CR, PR and SD at 4 months) will be compared using 
Pearson’s chi-square test, or if 20% or more of the expected cell frequencies are less than 5, Fisher’s 
exact test. Investigator reported outcomes as assessed by the ECOG PS will be analyzed using 
analysis of covariance. 
Subjects in each group will be stratified according to their initial PS (ECOG PS 0-1 vs 2) and whether 
they had progressed in less than or greater than 90 days after their initial chemotherapy. 
Sample Size Justification: 
Power calculations and subject numbers were calculated based on the primary endpoint of PFS.  
Reviewing the literature for studies that have evaluated topotecan as treatment for patients that have 
relapsed or not responded to first line therapies, it is estimated that the median PFS for the topotecan 
group will be 3.5 months and that the median PFS for the aldoxorubicin group will be 6.5 months.  
Based on the use of a two-sided log rank test at the α=0.05 level of significance, a total of 110 PFS 
events will be required for 90% power to detect this difference.  Assuming an 18 month accrual period 
and a 6 month follow-up period after enrollment of the last subject, approximately 132 subjects will be 
needed to achieve the total of 110 PFS events. 
Safety:  
The safety data will be summarized by treatment group.  The treatment groups will be compared with 
respect to occurrence of each AE. Total number of AEs leading to withdrawal, and abnormal 
laboratory tests will be compared between groups using Fisher’s exact test. Adverse events, ability to 
remain on assigned treatment (tolerability), and abnormal findings on physical examinations, vital 
signs, weight, ECG results, laboratory test results, and use of concomitant medications, will be 
assessed to characterize the safety profile of the treatment regimens. Descriptive statistics 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-SCLC-01 
June 20, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 56 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-28 Days 
Cycle 
1 
Cycle 
2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycle 8 
(repeat until 
off drug) 
Day 15      
(± 3 days) 
each Cycle 
Weeks 
27 & 33 
End of 
Treatment14 
Every 
12 
weeks13 
Follow 
Up12 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X16 
X 
 
Height (cm) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
BSA calculation2 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Vital signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
CT/ MRI scan / tumor measurements4 
X8a 
 
 
X8 
 
X8 
 
X8 
 
 
X8 
X8, 10 
X8 
 
ECG18 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X11 
X11 
 
ECHO (with ejection fraction)19  
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
 
CBC w/differential & plts5, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
 
X11 
X21 
 
Serum chemistries6, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
 
X11 
 
 
Urinalysis7 
X 
 
 
 
 
 
 
 
 
 
 
X11 
 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X15 
 
 
 
 
 
 
 
 
 
 
 
 
Aldoxorubicin administration17 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Topotecan 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Concomitant medications 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
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 7 for details). 


CLINICAL PROTOCOL 
TITLE: 
A Multicenter, Randomized, Open-Label Phase 2b Study 
to Investigate the Efficacy and Safety of Aldoxorubicin 
Compared to Topotecan in Subjects with Metastatic 
Small Cell Lung Cancer Who Either Relapsed or Were 
Refractory to Prior Chemotherapy 
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-SCLC-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
75,478 
EUDRACT NUMBER: 
2014-002189-64 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd., Suite 650 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY FAX: 
United States: 1-800-361-9714 
Italy: 02-4074-6066 (Milan) 
Spain: 900-804-637 
Hungary: 06-80-10-2323 or 00-800-8000-0723 
SAFETY EMAIL: 
safetydesk@psi-cro.com 
DATE OF PROTOCOL: 
June 20, 2014 
AMENDMENT 1: 
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-SCLC-01 Amendment 1 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
Protocol Synopsis 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Title of the Protocol:  
A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of 
Aldoxorubicin Compared to Topotecan in Subjects with Metastatic Small Cell Lung Cancer Who 
Either Relapsed or Were Refractory to Prior Chemotherapy 
Primary Objective: 
The primary objective of this study is to determine the efficacy of administration of aldoxorubicin 
compared to topotecan in subjects with metastatic small cell lung cancer (SCLC) who have relapsed 
or were refractory to prior chemotherapy, as measured by progression-free survival (PFS). 
Secondary Objectives: 
The secondary objectives of this study are to evaluate the efficacy of aldoxorubicin as measured by 
overall survival (OS), safety of aldoxorubicin compared to topotecan 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, as well as disease control rate and tumor response. 
Study Rationale and Significance: 
Aldoxorubicin (INNO-206; DOXO-EMCH) 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 antitumor activity with reduced toxicity in several murine models when 
compared with free doxorubicin. 
Patients with metastatic SCLC who have failed prior chemotherapies have a poor prognosis with 
response rates of <10-25%, PFS of around  2-4 months and median OS of approximately 6-10 
months, depending on the initial duration of response to first line treatment.  Several chemotherapy 
regimens have been explored as palliative therapy for subjects with these patients and include such 
agents as topotecan (only approved agent in the US), topotecan plus platinum, cyclophosphamide + 
doxorubicin + vincristine (CAV) and amirubicin (not approved in US). However, these regimens can 
be quite toxic and have not significantly impacted either PFS or OS in these individuals.  
Aldoxorubicin may improve upon the activity of these drugs without an increase in toxicity as has 
been demonstrated in animal studies. 


ALDOXORUBICIN-P2-SCLC-01 Amendment 1 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Study Design and Methodology: 
This is a phase 2b open-label study evaluating the efficacy and safety of aldoxorubicin administered 
at 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21 days compared to 
topotecan administered either IV at doses of 1.5 mg/m2/day for 5 consecutive days starting on Day 1, 
and repeated every 21 days, or 4 mg/m2 administered as a 30 min IV infusion on Days 1, 8 and 15 
every 28 days. Subjects will be randomized 1:1 to receive either aldoxorubicin or topotecan. 
Pretreatment with granulocyte colony-stimulating factor (G-CSF) is permitted according to ASCO 
Guidelines (Appendix E).[31]  
Subjects will visit the study site on Day 1 of each cycle. Safety monitoring, including AEs, a directed 
physical examination, laboratory evaluations (serum chemistry, complete blood count [CBC], and 
urinalysis), vital signs, weight measurements, Eastern Cooperative Group performance status (ECOG 
PS) and ECGs will be performed on Day 1 of each cycle (for all subjects).  They will have CBCs and 
serum chemistries on Day 15 (± 1 day) of each cycle as well. Cardiac function will also be followed 
periodically (per schedule of evaluations) with ECHO for subjects receiving aldoxorubicin. Treatment 
will continue until tumor progression is observed, subject asks to withdraw, or unacceptable toxicity 
occurs.  
Tumor response will be monitored at baseline, every 6 weeks from Cycle 1-Day 1 through week 36, 
and then every 12 weeks until disease progression using the Response Evaluation Criteria in Solid 
Tumors (RECIST) 1.1 criteria.[22] Overall survival, PFS, and PFS at 4 and 6 months will be evaluated. 
Objective response rate (ORR; complete response [CR] and partial response [PR]), disease control 
rate (ORR plus stable disease [SD] at 4 months) and quality of life (ECOG PS) will be assessed.  
 


ALDOXORUBICIN-P2-SCLC-01 Amendment 1 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
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 male or female. 
2. Histological confirmation of SCLC. 
3. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable 
by either surgery or radiation. 
4. Capable of providing informed consent and complying with trial procedures. 
5. ECOG PS 0-2. 
6. Life expectancy >8 weeks. 
7. Measurable tumor lesions according to RECIST 1.1 criteria.[22] 
8. 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.) 
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective 
contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual 
period of the female partner during the study treatment and for 6 months after the final dose of 
study treatment. 
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the 
Screening Visit and be non-lactating. 
11. Accessibility to the site that ensures the subject will be able to keep all study-related 
appointments. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin. 
2. Prior treatment with topotecan.   
3. Palliative surgery and/or radiation treatment < 21 days prior to date of randomization. 
4. Exposure to any investigational agent within 30 days of date of randomization. 
5. Exposure to any systemic chemotherapy within 21 days of date of randomization. 
6. Active (symptomatic) central nervous system (CNS) metastasis.  
7. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell 
carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless 
documented free of cancer for ≥3 years. 
8. Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine 
aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin 
>2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, 
hemoglobin <9 g/dL, albumin <2 gm/dL. 
9. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (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 F). 


ALDOXORUBICIN-P2-SCLC-01 Amendment 1 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
11. Baseline QTc >470 msec measured by Fridericia’s formula (QTcF) and/or previous history of QT 
prolongation while taking other medications. Concomitant use of medications associated with a 
high incidence of QT prolongation is not allowed. 
12. History or signs of active coronary artery disease with angina pectoris within the last 6 months. 
13. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) below the institution’s lower limit of predicted normal. 
14. Known history of HIV infection. 
15. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-
fungals. 
16. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, 
saquinavir. 
17. Major surgery within 30 days prior to date of randomization. 
18. Substance abuse or 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: 
Approximately 132 subjects with metastatic SCLC who have either not responded to or have 
progressed after treatment with no more than 1 prior systemic regimens will be randomized 1:1 
(aldoxorubicin:topotecan) at approximately 30 study centers in the US and Europe. The 
randomization will be stratified according to their initial PS (ECOG PS 0-1 vs 2), and whether they 
had relapsed < or > 90 days after completing their initial therapy. 
Test Product and Mode of Administration: 
Aldoxorubicin: Lyophilized powder in vials that contain 200 mg of aldoxorubicin reconstituted by 
adding a solution of 50% ethanol: 50% sterile water, administration completed within 2 hours (of 
being reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total dose of 
230 mg/m2 (170 mg/m2 doxorubicin equivalent). 
Topotecan:  
Topotecan for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder 
available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of 
topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is 
intended for administration by intravenous infusion (IVI). Each topotecan 4-mg vial is reconstituted 
with 4 mL Sterile Water for Injection. Then the appropriate volume of the reconstituted solution is 
diluted in either 0.9% Sodium Chloride IVI or 5% Dextrose IVI prior to administration. Because the 
lyophilized dosage form contains no antibacterial preservative, the reconstituted product should be 
used immediately.  
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 PFS at 4 and 6 months 
 OS 
 Objective tumor response (RECIST 1.1 criteria)[22] 
 Disease control rate (ORR + SD at 4 months) 
 Investigator assessment as measured by ECOG PS 


ALDOXORUBICIN-P2-SCLC-01 Amendment 1 
September 10, 2014 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Safety: 
The following safety variables will be assessed over the duration 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 will be evaluated for 
efficacy. All subjects who receive at least 1 dose of study medication will be evaluated for safety.  
Efficacy:   
The primary analysis of PFS will be carried out approximately 6 months following the completion of 
enrollment of 132 subjects. Survival distributions will be estimated using the Kaplan-Meier method 
and the 2 groups will be compared using a two-sided log rank test at the α=0.05 level of significance. 
The final analysis of OS will be completed when 110 OS events have occurred. Survival distributions 
will be estimated using the Kaplan-Meier method and the 2 groups will be compared using a two-
sided log rank test. 
Tumor response will be monitored at baseline, every 6 weeks from Cycle 1-Day 1 through week 36, 
and then every 12 weeks until disease progression. The percentage of subjects with CR or PR, or SD 
will be evaluated and the disease control rate (CR, PR and SD at 4 months) will be compared using 
Pearson’s chi-square test, or if 20% or more of the expected cell frequencies are less than 5, Fisher’s 
exact test. Investigator reported outcomes as assessed by the ECOG PS will be analyzed using 
analysis of covariance. 
Subjects in each group will be stratified according to their initial PS (ECOG PS 0-1 vs 2) and whether 
they had progressed in less than or greater than 90 days after their initial chemotherapy. 
Sample Size Justification: 
Power calculations and subject numbers were calculated based on the primary endpoint of PFS.  
Reviewing the literature for studies that have evaluated topotecan as treatment for patients that have 
relapsed or not responded to first line therapies, it is estimated that the median PFS for the topotecan 
group will be 3.5 months and that the median PFS for the aldoxorubicin group will be 6.5 months.  
Based on the use of a two-sided log rank test at the α=0.05 level of significance, a total of 110 PFS 
events will be required for 90% power to detect this difference.  Assuming an 18 month accrual period 
and a 6 month follow-up period after enrollment of the last subject, approximately 132 subjects will be 
needed to achieve the total of 110 PFS events. 
Safety:  
The safety data will be summarized by treatment group.  The treatment groups will be compared with 
respect to occurrence of each AE. Total number of AEs leading to withdrawal, and abnormal 
laboratory tests will be compared between groups using Fisher’s exact test. Adverse events, ability to 
remain on assigned treatment (tolerability), and abnormal findings on physical examinations, vital 
signs, weight, ECG results, laboratory test results, and use of concomitant medications, will be 
assessed to characterize the safety profile of the treatment regimens. Descriptive statistics 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-SCLC-01 Amendment 1 
September 10, 2014 
 
CytRx Corporation 
CONFIDENTIAL 
Page 56 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-28 Days 
Cycle 
1 
Cycle 
2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycle 8 
(repeat 
until off 
drug) 
Day 15    
(± 1 day) 
each Cycle 
End of 
Treatment14 
Every 
12 
weeks13 
Follow 
Up12 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X16 
X 
 
Height (cm) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
BSA calculation2 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Vital signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
CT/ MRI scan / tumor 
measurements4
X8a 
 
 
X8 
 
X8 
 
X8 
 
 
X8, 10 
X8 
 
ECG18 
X 
X 
X 
X 
X 
X 
X 
X 
X18 
 
X11 
X11 
 
ECHO (with ejection fraction)19  
X 
 
X 
 
X 
 
X 
 
X19 
 
X 
X 
 
CBC w/differential & plts5, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
X21 
 
Serum chemistries6, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
 
 
Urinalysis7 
X 
 
 
 
 
 
 
 
 
 
X11 
 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X15 
 
 
 
 
 
 
 
 
 
 
 
Aldoxorubicin administration17 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Topotecan 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Concomitant medications 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
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: 
A Multicenter, Randomized, Open-Label Phase 2b Study 
to Investigate the Efficacy and Safety of Aldoxorubicin 
Compared to Topotecan in Subjects with Metastatic 
Small Cell Lung Cancer Who Either Relapsed or Were 
Refractory to Prior Chemotherapy 
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-SCLC-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
75,478 
EUDRACT NUMBER: 
2014-002189-64 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd., Suite 650 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
United States: 1-877-412-8673 
Europe: +34 91 708 1250 ext. 41332 
 or 
+34 619 085 583
SAFETY FAX: 
United States: 1-877-853-3275 
Europe: + 34 91 307 60 47 
SAFETY EMAIL: 
drugsafety@pivotal.es 
DATE OF PROTOCOL: 
June 20, 2014 
AMENDMENT 1: 
September 10, 2014 
AMENDMENT 2: 
January 26, 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-SCLC-01 A2 
January 26, 2015 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
Protocol Synopsis 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Title of the Protocol:  
A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of 
Aldoxorubicin Compared to Topotecan in Subjects with Metastatic Small Cell Lung Cancer Who 
Either Relapsed or Were Refractory to Prior Chemotherapy 
Primary Objective: 
The primary objective of this study is to determine the efficacy of administration of aldoxorubicin 
compared to topotecan in subjects with metastatic small cell lung cancer (SCLC) who have relapsed 
or were refractory to prior chemotherapy, as measured by progression-free survival (PFS). 
Secondary Objectives: 
The secondary objectives of this study are to evaluate the efficacy of aldoxorubicin as measured by 
overall survival (OS), safety of aldoxorubicin compared to topotecan 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, as well as disease control rate and tumor response. 
Study Rationale and Significance: 
Aldoxorubicin (INNO-206; DOXO-EMCH) 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 antitumor activity with reduced toxicity in several murine models when 
compared with free doxorubicin. 
Patients with metastatic SCLC who have failed prior chemotherapies have a poor prognosis with 
response rates of <10-25%, PFS of around  2-4 months and median OS of approximately 6-10 
months, depending on the initial duration of response to first line treatment.  Several chemotherapy 
regimens have been explored as palliative therapy for subjects with these patients and include such 
agents as topotecan (only approved agent in the US), topotecan plus platinum, cyclophosphamide + 
doxorubicin + vincristine (CAV) and amirubicin (not approved in US). However, these regimens can 
be quite toxic and have not significantly impacted either PFS or OS in these individuals.  
Aldoxorubicin may improve upon the activity of these drugs without an increase in toxicity as has 
been demonstrated in animal studies. 


ALDOXORUBICIN-P2-SCLC-01 A2 
January 26, 2015 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Study Design and Methodology: 
This is a phase 2b open-label study evaluating the efficacy and safety of aldoxorubicin administered 
at 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21 days compared to 
topotecan administered either IV at doses of 1.5 mg/m2/day for 5 consecutive days starting on Day 1, 
and repeated every 21 days, or 4 mg/m2 administered as a 30 min IV infusion on Days 1, 8 and 15 
every 28 days. Subjects will be randomized 1:1 to receive either aldoxorubicin or topotecan. 
Treatment with granulocyte colony-stimulating factor (G-CSF) should be administered to all subjects 
as per investigator’s clinical judgment or according to ASCO Guidelines (Appendix E).[31]  Note:  
aldoxorubicin, at higher doses, has been associated with >20% incidence of grade 3 or 4 
neutropenia.  
Subjects will visit the study site on Day 1 of each cycle. Safety monitoring, including AEs, a directed 
physical examination, laboratory evaluations (serum chemistry and complete blood count [CBC]), vital 
signs, weight measurements, Eastern Cooperative Group performance status (ECOG PS) and ECGs 
will be performed on Day 1 of each cycle (for all subjects).  Subjects receiving aldoxorubicin will have 
blood drawn for serum electrolytes to evaluate the anion gap prior to each drug administration. They 
will have CBCs and serum chemistries on Day 15 (± 1 day) of each cycle as well. Cardiac function 
will also be followed periodically (per schedule of evaluations) with ECHO for subjects receiving 
aldoxorubicin. Treatment will continue until tumor progression is observed, subject asks to withdraw, 
or unacceptable toxicity occurs.  
Tumor response will be monitored at baseline, every 6 weeks (±5 days) from Cycle 1-Day 1 through 
week 36, and then every 12 weeks (±5 days) until disease progression using the Response 
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.[22] Overall survival, PFS, and PFS at 4 and 
6 months will be evaluated. Objective response rate (ORR; complete response [CR] and partial 
response [PR]), disease control rate (ORR plus stable disease [SD] at 4 months) and quality of life 
(ECOG PS) will be assessed.  
 


ALDOXORUBICIN-P2-SCLC-01 A2 
January 26, 2015 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
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 male or female. 
2. Histological confirmation of SCLC. 
3. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable 
by either surgery or radiation. 
4. Capable of providing informed consent and complying with trial procedures. 
5. ECOG PS 0-2. 
6. Life expectancy >8 weeks. 
7. Measurable tumor lesions according to RECIST 1.1 criteria.[22] 
8. 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.) 
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective 
contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual 
period of the female partner during the study treatment and for 6 months after the final dose of 
study treatment. 
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the 
Screening Visit and be non-lactating. 
11. Accessibility to the site that ensures the subject will be able to keep all study-related 
appointments. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin. 
2. Prior treatment with topotecan.   
3. Palliative surgery and/or radiation treatment < 21 days prior to date of randomization. 
4. Exposure to any investigational agent within 30 days of date of randomization. 
5. Exposure to any systemic chemotherapy within 21 days of date of randomization. 
6. Active (symptomatic) central nervous system (CNS) metastasis.  
7. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell 
carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless 
documented free of cancer for ≥3 years. 
8. Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine 
aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin 
>2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, 
hemoglobin <9 g/dL, albumin <2 gm/dL. 
9. Anion gap > 16 meq/L or arterial blood pH < 7.30. 
10. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (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 F). 


ALDOXORUBICIN-P2-SCLC-01 A2 
January 26, 2015 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
12. Baseline QTc >470 msec measured by Fridericia’s formula (QTcF) and/or previous history of QT 
prolongation while taking other medications. Concomitant use of medications associated with a 
high incidence of QT prolongation is not allowed. 
13. History or signs of active coronary artery disease with angina pectoris within the last 6 months. 
14. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) below the institution’s lower limit of predicted normal. 
15. Known history of HIV infection. 
16. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-
fungals. 
17. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, 
saquinavir. 
18. Major surgery within 30 days prior to date of randomization. 
19. Substance abuse or any condition that might interfere with the subject’s participation in the study 
or in the evaluation of the study results. 
20. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Approximately 132 subjects with metastatic SCLC who have either not responded to or have 
progressed after treatment with no more than 1 prior systemic regimens will be randomized 1:1 
(aldoxorubicin:topotecan) at approximately 40 study centers in the US and Europe. The 
randomization will be stratified according to their initial PS (ECOG PS 0-1 vs 2), and whether they 
had relapsed < or > 90 days after completing their initial therapy. 
Test Product and Mode of Administration: 
Aldoxorubicin: Lyophilized powder in vials that contain 200 mg of aldoxorubicin reconstituted by 
adding a solution of 50% ethanol: 50% sterile water, administration completed within 2 hours (of 
being reconstituted) as a 30 minute IV infusion in Lactated Ringer’s solution.  Total dose of 
230 mg/m2 (170 mg/m2 doxorubicin equivalent). 
Topotecan:  
Topotecan for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder 
available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of 
topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is 
intended for administration by intravenous infusion (IVI). Each topotecan 4-mg vial is reconstituted 
with 4 mL Sterile Water for Injection. Then the appropriate volume of the reconstituted solution is 
diluted in either 0.9% Sodium Chloride IVI or 5% Dextrose IVI prior to administration. Because the 
lyophilized dosage form contains no antibacterial preservative, the reconstituted product should be 
used immediately.  
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 PFS at 4 and 6 months 
 OS 
 Objective tumor response (RECIST 1.1 criteria)[22] 
 Disease control rate (ORR + SD at 4 months) 
 Investigator assessment as measured by ECOG PS 


ALDOXORUBICIN-P2-SCLC-01 A2 
January 26, 2015 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Safety: 
The following safety variables will be assessed over the duration 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 will be evaluated for 
efficacy. All subjects who receive at least 1 dose of study medication will be evaluated for safety.  
Efficacy:   
The primary analysis of PFS will be carried out approximately 6 months following the completion of 
enrollment of 132 subjects. Survival distributions will be estimated using the Kaplan-Meier method 
and the 2 groups will be compared using a two-sided log rank test at the α=0.05 level of significance. 
The final analysis of OS will be completed when 110 OS events have occurred. Survival distributions 
will be estimated using the Kaplan-Meier method and the 2 groups will be compared using a two-
sided log rank test. 
Tumor response will be monitored at baseline, every 6 weeks (±5 days) from Cycle 1-Day 1 through 
week 36, and then every 12 weeks (±5 days) until disease progression. The percentage of subjects 
with CR or PR, or SD will be evaluated and the disease control rate (CR, PR and SD at 4 months) will 
be compared using Pearson’s chi-square test, or if 20% or more of the expected cell frequencies are 
less than 5, Fisher’s exact test. Investigator reported outcomes as assessed by the ECOG PS will be 
analyzed using analysis of covariance. 
Subjects in each group will be stratified according to their initial PS (ECOG PS 0-1 vs 2) and whether 
they had progressed in less than or greater than 90 days after their initial chemotherapy. 
Sample Size Justification: 
Power calculations and subject numbers were calculated based on the primary endpoint of PFS.  
Reviewing the literature for studies that have evaluated topotecan as treatment for patients that have 
relapsed or not responded to first line therapies, it is estimated that the median PFS for the topotecan 
group will be 3.5 months and that the median PFS for the aldoxorubicin group will be 6.5 months.  
Based on the use of a two-sided log rank test at the α=0.05 level of significance, a total of 110 PFS 
events will be required for 90% power to detect this difference.  Assuming an 18 month accrual period 
and a 6 month follow-up period after enrollment of the last subject, approximately 132 subjects will be 
needed to achieve the total of 110 PFS events. 
Safety:  
The safety data will be summarized by treatment group.  The treatment groups will be compared with 
respect to occurrence of each AE. Total number of AEs leading to withdrawal, and abnormal 
laboratory tests will be compared between groups using Fisher’s exact test. Adverse events, ability to 
remain on assigned treatment (tolerability), and abnormal findings on physical examinations, vital 
signs, weight, ECG results, laboratory test results, and use of concomitant medications, will be 
assessed to characterize the safety profile of the treatment regimens. Descriptive statistics 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-SCLC-01 A2 
January 26, 2015 
 
CytRx Corporation 
CONFIDENTIAL 
Page 58 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-28 Days 
Cycle 
1 
Cycle 
2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycle 8 
(repeat 
until off 
drug) 
Day 15    
(± 1 day) 
each Cycle 
End of 
Treatment14 
Every 
12 
weeks13 
Follow 
Up12 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Height (cm) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
BSA calculation2 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Vital signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
CT/ MRI scan / tumor 
measurements4 
X8a 
 
 
X8 
 
X8 
 
X8 
 
 
X8, 10 
X8 
 
ECG18 
X 
X 
X 
X 
X 
X 
X 
X 
X18 
 
X11 
X11 
 
ECHO (with ejection fraction)19  
X 
 
X 
 
X 
 
X 
 
X19 
 
X 
X 
 
CBC w/differential & plts5, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
X21 
 
Serum chemistries6, 20 
X* 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
 
 
Urinalysis7 
X 
 
 
 
 
 
 
 
 
 
X11 
 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X15 
 
 
 
 
 
 
 
 
 
 
 
Aldoxorubicin administration17 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Topotecan 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Concomitant medications 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
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: 
A Multicenter, Randomized, Open-Label Phase 2b Study 
to Investigate the Efficacy and Safety of Aldoxorubicin 
Compared to Topotecan in Subjects with Metastatic 
Small Cell Lung Cancer Who Either Relapsed or Were 
Refractory to Prior Chemotherapy 
PROTOCOL NUMBER: 
ALDOXORUBICIN-P2-SCLC-01 
STUDY DRUG: 
Aldoxorubicin 
IND NUMBER: 
75,478 
EUDRACT NUMBER: 
2014-002189-64 
SPONSOR:  
CytRx Corporation 
11726 San Vicente Blvd., Suite 650 
Los Angeles, CA 90049 
(310) 826-5648
FAX: (310) 826-6139
SAFETY HOTLINE: 
United States: 1-877-412-8673 
Europe: +34 91 708 1250 ext. 41332 
 or 
+34 619 085 583
SAFETY FAX: 
United States: 1-877-853-3275 
Europe: + 34 91 307 60 47 
SAFETY EMAIL: 
drugsafety@pivotal.es 
DATE OF PROTOCOL: 
June 20, 2014 
AMENDMENT 1: 
September 10, 2014 
AMENDMENT 2: 
January 26, 2015 
AMENDMENT 3: 
February 17, 2016 
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-SCLC-01 A3 
February 17, 2016 
CytRx Corporation 
CONFIDENTIAL 
Page 3 
Protocol Synopsis 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Title of the Protocol:  
A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of 
Aldoxorubicin Compared to Topotecan in Subjects with Metastatic Small Cell Lung Cancer Who 
Either Relapsed or Were Refractory to Prior Chemotherapy 
Primary Objective: 
The primary objective of this study is to determine the efficacy of administration of aldoxorubicin 
compared to topotecan in subjects with metastatic small cell lung cancer (SCLC) who have relapsed 
or were refractory to prior chemotherapy, as measured by progression-free survival (PFS). 
Secondary Objectives: 
The secondary objectives of this study are to evaluate the efficacy of aldoxorubicin as measured by 
overall survival (OS), safety of aldoxorubicin compared to topotecan 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, as well as disease control rate and tumor response. 
Study Rationale and Significance: 
Aldoxorubicin (INNO-206; DOXO-EMCH) 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 antitumor activity with reduced toxicity in several murine models when 
compared with free doxorubicin. 
Patients with metastatic SCLC who have failed prior chemotherapies have a poor prognosis with 
response rates of <10-25%, PFS of around  2-4 months and median OS of approximately 6-10 
months, depending on the initial duration of response to first line treatment.  Several chemotherapy 
regimens have been explored as palliative therapy for subjects with these patients and include such 
agents as topotecan (only approved agent in the US), topotecan plus platinum, cyclophosphamide + 
doxorubicin + vincristine (CAV) and amirubicin (not approved in US). However, these regimens can 
be quite toxic and have not significantly impacted either PFS or OS in these individuals.  
Aldoxorubicin may improve upon the activity of these drugs without an increase in toxicity as has 
been demonstrated in animal studies. 


ALDOXORUBICIN-P2-SCLC-01 A3 
February 17, 2016 
CytRx Corporation 
CONFIDENTIAL 
Page 4 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Study Design and Methodology: 
This is a phase 2b open-label study evaluating the efficacy and safety of aldoxorubicin administered 
at 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21 days compared to 
topotecan administered either IV at doses of 1.5 mg/m2/day for 5 consecutive days starting on Day 1, 
and repeated every 21 days, or 4 mg/m2 administered as a 30 min IV infusion on Days 1, 8 and 15 
every 28 days. Subjects will be randomized 1:1 to receive either aldoxorubicin or topotecan. 
Treatment with granulocyte colony-stimulating factor (G-CSF) should be administered to all subjects 
as per investigator’s clinical judgment or according to ASCO Guidelines (Appendix E).[31]  Note:  
aldoxorubicin, at higher doses, has been associated with >20% incidence of grade 3 or 4 
neutropenia.  
Subjects will visit the study site on Day 1 of each cycle. Safety monitoring, including AEs, a directed 
physical examination, laboratory evaluations (serum chemistry and complete blood count [CBC]), vital 
signs, weight measurements, Eastern Cooperative Group performance status (ECOG PS) and ECGs 
will be performed on Day 1 of each cycle (for all subjects).  Subjects receiving aldoxorubicin will have 
blood drawn for serum electrolytes to evaluate the anion gap prior to each drug administration. They 
will have CBCs and serum chemistries on Day 15 (± 1 day) of each cycle as well. Cardiac function 
will also be followed periodically (per schedule of evaluations) with ECHO for subjects receiving 
aldoxorubicin. Treatment will continue until tumor progression is observed, subject asks to withdraw, 
or unacceptable toxicity occurs.  
Tumor response will be monitored at baseline, every 6 weeks (± 5 days) from Cycle 1-Day 1 through 
week 36, and then every 12 weeks (± 5 days) until disease progression using the Response 
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.[22] Overall survival, PFS, and PFS at 4 and 
6 months will be evaluated. Objective response rate (ORR; complete response [CR] and partial 
response [PR]), disease control rate (ORR plus stable disease [SD] at 4 months) and quality of life 
(ECOG PS) will be assessed.  
 


ALDOXORUBICIN-P2-SCLC-01 A3 
February 17, 2016 
CytRx Corporation 
CONFIDENTIAL 
Page 5 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
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 male or female. 
2. Histological confirmation of SCLC. 
3. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable 
by either surgery or radiation. 
4. Capable of providing informed consent and complying with trial procedures. 
5. ECOG PS 0-2. 
6. Life expectancy >8 weeks. 
7. Measurable tumor lesions according to RECIST 1.1 criteria.[22] 
8. 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.) 
9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective 
contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual 
period of the female partner during the study treatment and for 6 months after the final dose of 
study treatment. 
10. Women of child bearing potential must have a negative serum or urine pregnancy test at the 
Screening Visit and be non-lactating. 
11. Accessibility to the site that ensures the subject will be able to keep all study-related 
appointments. 
Exclusion Criteria: 
Subjects meeting the following criteria will not be enrolled: 
1. Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin. 
2. Prior treatment with topotecan.   
3. Palliative surgery and/or radiation treatment < 14 days prior to date of randomization. 
4. Exposure to any investigational agent within 30 days of date of randomization. 
5. Exposure to any systemic chemotherapy within 21 days of date of randomization. 
6. Active (symptomatic) central nervous system (CNS) metastasis.  
7. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell 
carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless 
documented free of cancer for ≥3 years. 
8. Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine 
aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin 
>2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, 
hemoglobin <9 g/dL, albumin <2 gm/dL. 
9. Anion gap >16 meq/L or arterial blood pH <7.30. 
10. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association 
(NYHA) guidelines (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 F). 


ALDOXORUBICIN-P2-SCLC-01 A3 
February 17, 2016 
CytRx Corporation 
CONFIDENTIAL 
Page 6 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
12. Baseline QTc >470 msec measured by Fridericia’s formula (QTcF) and/or previous history of QT 
prolongation while taking other medications. Concomitant use of medications associated with a 
high incidence of QT prolongation is not allowed. 
13. History or signs of active coronary artery disease with angina pectoris within the last 6 months. 
14. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) below the institution’s lower limit of predicted normal. 
15. Known history of HIV infection. 
16. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-
fungals. 
17. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, 
saquinavir. 
18. Major surgery within 30 days prior to date of randomization. 
19. Substance abuse or any condition that might interfere with the subject’s participation in the study 
or in the evaluation of the study results. 
20. Any condition that is unstable and could jeopardize the subject’s participation in the study. 
Number of Subjects: 
Approximately 132 subjects with metastatic SCLC who have either not responded to or have 
progressed after treatment with no more than 1 prior systemic regimens will be randomized 1:1 
(aldoxorubicin:topotecan) at approximately 40 study centers in the US and Europe. The 
randomization will be stratified according to their initial PS (ECOG PS 0-1 vs 2), and whether they 
had relapsed < or > 90 days after completing their initial therapy. 
Test Product and Mode of Administration: 
Aldoxorubicin: Lyophilized powder in vials that contain 200 mg of aldoxorubicin reconstituted by 
adding a solution of 50% ethanol: 50% sterile water, administration completed within 2 hours (of 
being reconstituted) as an approximate 30 minute IV infusion in Lactated Ringer’s solution.  Total 
dose of 230 mg/m2 (170 mg/m2 doxorubicin equivalent). 
Topotecan:  
Topotecan for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder 
available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of 
topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is 
intended for administration by intravenous infusion (IVI). Each topotecan 4-mg vial is reconstituted 
with 4 mL Sterile Water for Injection. Then the appropriate volume of the reconstituted solution is 
diluted in either 0.9% Sodium Chloride IVI or 5% Dextrose IVI prior to administration. Because the 
lyophilized dosage form contains no antibacterial preservative, the reconstituted product should be 
used immediately.  
Criteria for Evaluation: 
Efficacy: 
The following efficacy variables will be evaluated as noted: 
 PFS 
 PFS at 4 and 6 months 
 OS 
 Objective tumor response (RECIST 1.1 criteria)[22] 
 Disease control rate (ORR + SD at 4 months) 
 Investigator assessment as measured by ECOG PS 


ALDOXORUBICIN-P2-SCLC-01 A3 
February 17, 2016 
CytRx Corporation 
CONFIDENTIAL 
Page 7 
Name of Sponsor/Company: CytRx Corporation 
 
Protocol Number:  
ALDOXORUBICIN-P2-SCLC-01 
Phase of Development: 2b 
 
Safety: 
The following safety variables will be assessed over the duration 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 will be evaluated for 
efficacy. All subjects who receive at least 1 dose of study medication will be evaluated for safety.  
Efficacy:   
The primary analysis of PFS will be carried out when 110 PFS events have occurred, approximately 6 
months following the completion of enrollment of 132 subjects. Survival distributions will be estimated 
using the Kaplan-Meier method and the 2 groups will be compared using a two-sided, unstratified log 
rank test at the α=0.05 level of significance. 
Tumor response will be monitored at baseline, every 6 weeks (± 5 days) from Cycle 1-Day 1 through 
week 36, and then every 12 weeks (± 5 days) until disease progression. The percentage of subjects 
with CR or PR, or SD will be evaluated and the disease control rate (CR, PR and SD at 4 months) will 
be compared using Pearson’s chi-square test, or if 20% or more of the expected cell frequencies are 
less than 5, Fisher’s exact test. Investigator reported outcomes as assessed by the ECOG PS will be 
analyzed using analysis of covariance. 
Subjects in each group will be stratified according to their initial PS (ECOG PS 0-1 vs 2) and whether 
they had progressed in less than or greater than 90 days after their initial chemotherapy. 
Sample Size Justification: 
Power calculations and subject numbers were calculated based on the primary endpoint of PFS.  
Reviewing the literature for studies that have evaluated topotecan as treatment for patients that have 
relapsed or not responded to first line therapies, it is estimated that the median PFS for the topotecan 
group will be 3.5 months and that the median PFS for the aldoxorubicin group will be 6.5 months.  
Based on the use of a two-sided log rank test at the α=0.05 level of significance, a total of 110 PFS 
events will be required for 90% power to detect this difference.  Assuming an 18 month accrual period 
and a 6 month follow-up period after enrollment of the last subject, approximately 132 subjects will be 
needed to achieve the total of 110 PFS events. 
Safety:  
The safety data will be summarized by treatment group.  The treatment groups will be compared with 
respect to occurrence of each AE. Total number of AEs leading to withdrawal, and abnormal 
laboratory tests will be compared between groups using Fisher’s exact test. Adverse events, ability to 
remain on assigned treatment (tolerability), and abnormal findings on physical examinations, vital 
signs, weight, ECG results, laboratory test results, and use of concomitant medications, will be 
assessed to characterize the safety profile of the treatment regimens. Descriptive statistics 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-SCLC-01 A3 
February 17, 2016 
 
CytRx Corporation 
CONFIDENTIAL 
Page 59 
APPENDIX A: Schedule of Treatment and Evaluations 
 
Screening 
-28 Days 
Cycle 
1 
Cycle 
2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7 
Cycle 8 
(repeat 
until off 
drug) 
Day 15    
(± 1 day) 
each Cycle 
End of 
Treatment14 
Every 
12 
weeks13 
Follow 
Up12 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Height (cm) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
BSA calculation2 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Vital signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
CT/ MRI scan / tumor 
measurements4 
X8a 
 
 
X8 
 
X8 
 
X8 
 
 
X8, 10 
X8 
 
ECG18 
X 
X 
X 
X 
X 
X 
X 
X 
X18 
 
X11 
X11 
 
ECHO (with ejection fraction)19  
X 
 
X 
 
X 
 
X 
 
X19 
 
X22 
X 
 
CBC w/differential & plts5, 20 
X 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
X21 
 
Serum chemistries6, 20 
X* 
X16 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
 
 
Urinalysis7 
X 
 
 
 
 
 
 
 
 
 
X11 
 
 
Serum/urine pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X15 
 
 
 
 
 
 
 
 
 
 
 
Aldoxorubicin administration17 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Topotecan 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Concomitant medications 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
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.