Metastatic Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGAldoxorubicin
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.
DRUGTopotecan
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
Sponsors
ImmunityBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 24 months | 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. Progressive Disease is defined as: ≥20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥1 new lesion is also considered progression. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-related Toxicities (Adverse Events) | Treatment was planned to continue until tumor progression is observed, subject asks to withdraw, or unacceptable toxicity occurs, up to 451 days. |
Countries
Hungary, Spain, United States
Participant flow
Pre-assignment details
135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start.
Participants by arm
| Arm | Count |
|---|---|
| Aldoxorubicin Aldoxorubicin: 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. | 69 |
| Topotecan Topotecan: 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 | 66 |
| Total | 135 |
Baseline characteristics
| Characteristic | Aldoxorubicin | Total | Topotecan |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 6.73 | 64.42 years STANDARD_DEVIATION 0 | 63.5 years STANDARD_DEVIATION 7.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 117 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 126 Participants | 62 Participants |
| Sex: Female, Male Female | 34 Participants | 60 Participants | 26 Participants |
| Sex: Female, Male Male | 35 Participants | 75 Participants | 40 Participants |
| Subjects with Metastatic Small Cell Lung Cancer | 69 Participants | 135 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 57 / 69 | 50 / 66 |
| other Total, other adverse events | 61 / 67 | 61 / 63 |
| serious Total, serious adverse events | 17 / 67 | 18 / 63 |
Outcome results
Primary
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. Progressive Disease is defined as: ≥20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥1 new lesion is also considered progression.
Time frame: 24 months
Population: PFS is measured from randomization, not from treatment start date. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aldoxorubicin | Progression-Free Survival (PFS) | 1.5 Months |
| Topotecan | Progression-Free Survival (PFS) | 2.7 Months |
Secondary
Number of Participants With Treatment-related Toxicities (Adverse Events)
Time frame: Treatment was planned to continue until tumor progression is observed, subject asks to withdraw, or unacceptable toxicity occurs, up to 451 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aldoxorubicin | Number of Participants With Treatment-related Toxicities (Adverse Events) | 51 Participants |
| Topotecan | Number of Participants With Treatment-related Toxicities (Adverse Events) | 52 Participants |