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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metastatic Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Aldoxorubicin
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years male or female. Histological confirmation of SCLC. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable by either surgery or radiation. Capable of providing informed consent and complying with trial procedures. ECOG PS 0-2. Life expectancy >8 weeks. Measurable tumor lesions according to RECIST 1.1 criteria.[22] 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.) 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. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Accessibility to the site that ensures the subject will be able to keep all study-related appointments. Exclusion Criteria: Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin. Prior treatment with topotecan. Palliative surgery and/or radiation treatment < 21 days prior to date of randomization. Exposure to any investigational agent within 30 days of date of randomization. Exposure to any systemic chemotherapy within 21 days of date of randomization. Active (symptomatic) central nervous system (CNS) metastasis. 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. 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. Anion gap > 16 meq/L or arterial blood pH < 7.30. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association (NYHA) guidelines (Appendix D). 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). 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. History or signs of active coronary artery disease with angina pectoris within the last 6 months. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) below the institution's lower limit of predicted normal. Known history of HIV infection. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, saquinavir. Major surgery within 30 days prior to date of randomization. Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results. Any condition that is unstable and could jeopardize the subject's participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aldoxorubicin<br> | Drug: Aldoxorubicin<br>* 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.<br>* Other names: INNO-206;|
| Active Comparator: Topotecan<br> | Drug: Topotecan<br>* 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<br>* Other names: Hycamtin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is defined as the time from randomization to date of death. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive. | 36 months | 
| Safety Measures | The 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. | 24 months |