Small cell lung cancer

Primary Objective: Compare the efficacy of palifosfamide-tris in combination with carboplatin and etoposide (PaCE) chemotherapy to carboplatin and etoposide (CE) alone, as measured by overall survival (OS), in chemotherapy naïve subjects with extensive-stage small cell lung cancer (SCLC). Secondary Objectives: Assess secondary efficacy endpoints including progression free survival (PFS), objective response rate (ORR), response duration, and effects on quality of life (QOL) and disease-related symptoms. Assess potential prognostic factors for OS (i.e., performance status, age, and gender). Assess the safety of PaCE chemotherapy in the study population. Collect tumor tissue samples for future analysis of potential biomarkers that may correlate with objective tumor response and/or clinical outcome.

Palifosfamide-tris

Palifosfamide-tris

Injection

542 mg

Primary Efficacy Endpoint:
The primary efficacy variable, OS, is defined as the time from randomization to the date
of death.

Secondary Efficacy Endpoints:
PFS (progression free survival): Time from randomization to the date of PD or death (if prior to progression). Subjects without PD or death occurring as of the time of analysis will be censored as of the last date of disease evaluation.

Objective response rate (ORR): Proportion of subjects achieving a confirmed PR or CR according to RECIST v1.1 during study treatment or within 21 days following termination of study treatment. All objective responses (CR or PR) require confirmation by a repeat tumor assessment at least 4 weeks (28 days) after the response is first observed in order for the response to be considered confirmed.

Objective response duration: Time from the date of first objective response (PR or CR), with subsequent confirmation, until the date of PD or the occurrence of death (if death occurs earlier). Duration of response in subjects who have not progressed or died at the time of analysis will be censored as of the date of their last tumor assessment.

Inclusion criteria:
1. Male or female subjects, age ≥ 18 years.
2. Histological or cytological diagnosis of extensive-stage small cell lung cancer. (Note: Extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or
pericardial effusion or hematogenous metastases.)
3. No prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer. Exception: Prior radiotherapy for brain metastases is allowed provided that the subject has recovered from any acute treatment related toxicity.
4. Measurable or non-measureable disease as per RECIST v1.1 (Appendix 1).
5. ECOG Performance Status of 0, 1, or 2 (Appendix 2).
6. Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements:
a. Hemoglobin ≥10.0 g/dL
b. Absolute neutrophil count (ANC) ≥1,500/mm3
c. Platelet count ≥100,000/mm3
d. Total bilirubin ≤1.5 x upper limit of normal (ULN). For subjects with Gilbert’s Disease, Total bilirubin ≤3 x ULN
e. ALT and AST ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5×ULN
f. International Normalized Ratio (INR) ≤1.5, if not therapeutically anticoagulated. Subjects who are being therapeutically anticoagulated may be included provided that the anticoagulation regimen is stable and closely monitored.
g. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2 as determined using the Modification of Diet in Renal Disease (MDRD) equation (Appendix 3); in cases where the MDRD equation may not be suitable, a 24 hour urine creatinine clearance test may be
substituted with prior approval of the Medical Monitor.
7. Male and female subjects of child bearing potential must agree to use a double-barrier method of birth control from the screening visit through 6 months after the last dose of study drug.
8. Written informed consent in compliance with the Human Investigation Review Committee (IEC/IRB) having jurisdiction over the site.

Exclusion Criteria:
1. Exposure to any investigational agent within 30 days prior to randomization.
2. Previously untreated (non-irradiated), symptomatic brain metastases. No prior treatment is required for non-symptomatic brain metastases. Previously treated symptomatic brain
metastases are permitted.
3. Known allergy to any of the study drugs or their excipients.
4. Currently pregnant (confirmed with a positive serum pregnancy test) or nursing.
5. Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
6. Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy within 7 days prior to randomization. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.)
7. Major surgery or significant traumatic injury within 28 days of the time of randomization.
8. Presence of, or history of any illness or injury to the urinary tract (renal or post-renal) which may, in the opinion of the investigator, make the subject more susceptible to acute renal insufficiency.
9. Any malignancy other than small cell lung cancer within the last 5 years prior to randomization, with the exception of cervical carcinoma in situ, nonmelanoma skin cancer, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease. (Exception: Subjects with a history of malignancy other than SCLC may be enrolled after consultation with the medical monitor provided the patient’s prognosis is best defined by the ES-SCLC.)