Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer

Inclusion Criteria:

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:

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).

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.