Study of Picoplatin Efficacy After Relapse

A Randomized, Controlled Phase III Trial of Picoplatin and BSC Versus BSC Alone in Patients With Small Cell Lung Cancer (SCLC), Refractory or Progressive Within Six Months of Completing First-Line, Platinum-Containing Chemotherapy.

Picoplatin is a new type of platinum drug that has been investigated in several clinical trials, and may provide an improved safety profile over current treatment options. This study is designed to compare the efficacy and safety of picoplatin plus Best Supportive Care (BSC) with BSC alone. Best Supportive Care includes care and treatment to optimize the comfort of patients and their ability to function, as well as to minimize the side-effects of anti-cancer treatments.

This Phase 3 study will enroll subjects with Small Cell Lung Cancer (SCLC) who are refractory or progressive within 6 months of completing first-line, platinum-containing chemotherapy. Subjects will be centrally randomized 2:1 to receive picoplatin plus BSC every 3 weeks, or BSC alone. After discontinuation of picoplatin, all subjects will continue to receive BSC and will continue to be evaluated every 3 weeks until discontinuation from the study, death, or the end of the study. After discontinuation of picoplatin, subjects may be treated with another chemotherapy at their physician's discretion and then will be followed for survival.

Inclusion Criteria:

• Histological or cytological diagnosis of SCLC or combined SCLC/non-small cell lung cancer (NSCLC) defined as SCLC mixed with squamous cell carcinoma, adenocarcinoma, or large cell carcinoma.
• One and only 1 prior cisplatin or carboplatin-containing chemotherapy regimen for SCLC within the scope of the National Comprehensive Cancer Network (NCCN) Guidelines (Section 5.4.1).
• Radiological evidence of SCLC that never responded or progressed within 90 days after completion of first-line therapy (refractory); or responded initially to first-line therapy but progressed between 91 and 180 days after treatment was completed (progressed within 91 to 180 days).
• CT scans of head, chest and abdomen (including adrenal and full extent of liver) with contrast, preferably within 14 days prior to randomization (up to 21 days is allowed if necessary). MRI is acceptable in the case of allergy to contrast agents. The presence or absence of measurable disease gy RECIST must be documented from the baseline CT or MRI scan.
• Patients with brain metastases must have been treated with brain irradiation. Only patients wtih asymptomatic brain metastases are eligible for this study.
• ECOG PS 0, 1 or 2 within 3 days prior to randomization (Appendix II).
• Life expectancy of at least 8 weeks within 3 days prior to randomization.
• At least 21 days must have elapsed since the most recent prior chemotherapy dose, with evidence of hematological recovery.
• At least 14 days must have elapsed since the most recent prior radiotherapy dose.
• At least 14 days must have elapsed since prior surgery except for the placement of venous access device or bronchoscopy.
• Subject must be recovered to ≤ Grade 1 toxicity from all non-hematological adverse effects of prior therapies (excluding alopecia).
• Age 18 years or over.
• ANC ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L.
• Hemoglobin of ≥ 90 g/L (transfusion permitted to achieve this hemoglobin).
• Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN if liver involvement is present.
• Bilirubin of ≤ 1.5 times upper limit of normal (ULN).
• Blood urea nitrogen ≤ 1.5 times ULN (hypovolemic subjects may be hydrated to achieve this BUN).
• Creatinine clearance of ≥ 50 mL/min, as calculated by the Cockcroft-Gault formula (Appendix III).
• Women of childbearing potential must have a negative pregnancy test (serum or urine). Sexually active couples of child-bearing potential must agree to use appropriate birth control methods during chemotherapy and for 3 months after chemotherapy.
• Signed informed consent.

Exclusion Criteria:

• Prior radiotherapy that included ≥ 30% of the bone marrow (Appendix IV).
• Pleural effusion as the only radiological evidence of SCLC.
• Untreated or symptomatic brain or central nervous system (CNS) metastases.
• Grade 2 or higher peripheral neuropathy.
• Significant cardiac disease, defined as myocardial infarction within 3 months prior to randomization, congestive heart failure classified by the New York Heart Association as Class III or IV (Appendix V), uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.
• Serious medical or psychiatric illness that could potentially interfere with the completion of study treatment according to this protocol, e.g., active infection, Crohn's disease, ulcerative colitis, etc.
• Use of other investigational drugs within 30 days prior to randomization.
• Breast-feeding.
• History of any other malignancy within 5 years, with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix.