A Phase 2 Study Comparing TAS-102 Versus Topotecan or Amrubicin to Treat Small Cell Lung Cancer Following Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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The purpose of this trial is to compare the effects of TAS-102 with either amrubicin or topotecan (drugs used in Small Cell Lung Cancer) on lung cancer to find out the effects on survival, how much time may pass without disease progression, and the safety of TAS-102.

Detailed Description
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This is a multicenter, open-label, two-arm, randomized Phase 2 study of TAS-102 versus Investigator's choice of therapy in patients requiring second-line chemotherapy for SCLC refractory or sensitive to first-line platinum-based chemotherapy. Investigator's choice of therapy is defined as second-line chemotherapy with IV topotecan (Europe/Japan) or IV amrubicin (Japan). Patients will be stratified by response to first-line platinum-based chemotherapy (sensitive vs refractory). Sensitive patients are defined as patients who did not progress within 90 days after the last dose, and refractory patients are defined as patients who never responded or who responded but had radiologic progression < 90 days after the last dose.

Official Title
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An Open-Label, Randomized, Phase 2 Study Comparing TAS-102 Versus Topotecan or Amrubicin in Patients Requiring Second-Line Chemotherapy for Small Cell Lung Cancer That is Refractory or Sensitive to First-Line Platinum-Based Chemotherapy

Conditions
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Small Cell Lung Cancer (SCLC)

Intervention / Treatment
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* Drug: TAS-102
* Drug: Amrubicin (Japan)
* Drug: Topotecan (Japan/Europe)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has provided written informed consent Is ≥18 years of age for patients enrolled in Europe; or ≥20 years of age for patients enrolled in Japan Has definitive histologically or cytologically confirmed SCLC (limited or extensive disease) Has progressed or had recurrence within 30 days prior to randomization Has at least one measurable lesion, as defined by RECIST criteria version 1.1 ECOG performance status of 0, 1, or 2 Is able to take medications orally Has adequate organ function (bone marrow, kidney and liver) Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control. Exclusion Criteria: Has cerebral metastases (unless metastases have been treated and controlled, metastases have been stable for at least 2-months post-intervention, and patient is not receiving corticosteroid treatment) Certain serious illnesses or medical condition(s) Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration Has received TAS-102 Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies Is a pregnant or lactating female

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: TAS-102<br> | Drug: TAS-102<br>* 35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.<br>|
| Active Comparator: Investigator Choice of Amrubicin or Topotecan<br>Investigator Choice of Amrubicin (Japan only) or Topotecan (Europe and Japan) | Drug: Amrubicin (Japan)<br>* Patients will receive treatment administered according to the country-specific approved prescribing information<br>* Other names: Calsed;Drug: Topotecan (Japan/Europe)<br>* Patients will receive treatment administered according to the country-specific approved prescribing information<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 | Tumor assessments will be performed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6 weeks during study treatment, and every 8 weeks after treatment is completed. Tumor assessments will be performed from Day 1, Cycle 1 until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met. | Every 6 weeks from the start of study treatment (Day 1, Cycle 1). Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Survival status will be collected at 8-week intervals until death, for up to 12 months after the first dose of study medication for the last patient randomized or until the target number of events (deaths) is met, whichever is later. | 
| Safety monitoring including adverse events, vital signs, and laboratory assessments | Standard safety monitoring will be performed and adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 | Through 30 days following last administration of study medication or until initiation of new anticancer treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Second line Small Cell Lung Cancer, (SCLC), Refractory or Sensitive to First line Platinum based chemotherapy