Study of Palifosfamide-tris in Combination With Carboplatin and Etoposide in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer (The MATISSE Study)

Study Overview
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Brief Summary
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This is a multinational, multicenter, randomized controlled, open-label, adaptive study to evaluate the efficacy of PaCE chemotherapy in chemotherapy naive subjects with extensive-stage SCLC. Eligible subjects will be stratified according to age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status, and randomized in a 1:1 ratio to receive either PaCE or CE chemotherapy. The study design uses an adaptive group sequential approach with sample size re-estimation at the interim analysis. Secondary efficacy endpoints include ORR, PFS, duration of response and changes in QOL and disease-related symptoms. Tumor-related endpoints will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. The safety of study treatments will be assessed by the frequency and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. To provide an initial confirmation of safety, an early interim analysis of safety data only will be performed. An independent Data Monitoring Committee (DMC) will be convened to assess the safety and efficacy of the study interventions and to monitor the overall conduct of the clinical trial.

Official Title
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A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer. The MATISSE Study

Conditions
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Extensive-Stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Palifosfamide-tris
* Drug: Etoposide
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented extensive-stage small cell lung cancer. Patient has received no prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer. ECOG Performance Status of 0, 1 or 2. Adequate bone marrow and organ function based on the results of protocol- specified laboratory tests. Male and female patients must agree to use a highly reliable method of birth control during study participation. Able to provide informed consent Exclusion Criteria: Previously untreated (non-irradiated), symptomatic brain metastases. Known allergy to any of the study drugs or their excipients. Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol, based on screening tests, physical examination and medical history (as specifically defined in the clinical protocol). 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 small cell lung cancer may be enrolled after consultation with the medical monitor provided the patient's prognosis is best defined by the extensive-stage small cell lung cancer). Currently pregnant or nursing.

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: Palifosfamide-tris plus Carboplatin and Etoposide<br>Drug: palifosfamide-tris in combination with carboplatin and etoposide palifosfamide-tris: 130 mg/m2/day 3 days every 21 days for a max of 6 cycles. carboplatin: AUC 4 mg/mL/min 1 day every 21 days for a max of 6 cycles. etoposide: 100 mg/m2/day 3 days every 21 days for a max of 6 cycles. | Drug: Carboplatin<br>* AUC 4 mg/mL/min 1 day every 21 days for a max of 6 cycles.<br>Drug: Palifosfamide-tris<br>* 130 mg/m2/day 3 days every 21 days for a max of 6 cycles.<br>Drug: Etoposide<br>* 100 mg/m2/day 3 days every 21 days for a maximum of 6 cycles.<br>|
| Active Comparator: Carboplatin plus Etoposide<br>Drug: carboplatin in combination with etoposide carboplatin: AUC 5mg/mL/min 1 day every 21 days for a maximum of 6 cycles. etoposide: 100 mg/m2/day 3 days every 21 days for a maximum of 6 cycles. | Drug: Etoposide<br>* 100 mg/m2/day 3 days every 21 days for a maximum of 6 cycles.<br>Drug: Carboplatin<br>* AUC 5 mg/mL/min 1 day every 21 days for a max of 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Assessed every 12 weeks for survival until 1 year following completion of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Assessed every 6 weeks for 22 weeks, then every 12 weeks until progressive disease, initiation of alternate anticancer therapy, or 1 year following the last patient enrolled (whichever is soonest) | 
| Quality of Life (QOL) as assessed by EQ-5D-3L and QLQ-LC13 |  | Assessed every 3 weeks for 22 weeks, then every 12 weeks until 1 year following the last patient enrolled | 
| Objective Response Rate (ORR) |  | Assessed every 6 weeks for 22 weeks, then every 12 weeks until a partial or complete response is confirmed | 
| Response Duration |  | Time from the date of first objective response (partial or complete response), with subsequent confirmation, until the date of disease progression or the occurrence of death | 
| Safety parameters (number of adverse events as well as number of findings from physical examinations, ECGs, vital signs, and clinical laboratory results)using NCI CTCAE v. 4.03 |  | 22 weeks |