| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Small Cell Lung Cancer that is refractory or sensitive to first-line platinum-based chemotherapy. |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10041067 |
| E.1.2 | Term | Small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate Progression-free survival (PFS) for TAS-102 (experimental arm) and Investigator’s choice of IV topotecan or IV amrubicin (control arm) in patients requiring second-line chemotherapy for SCLC refractory or sensitive to first-line platinum-based chemotherapy |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the following endpoints for TAS-102 (experimental arm) and Investigator’s choice of IV topotecan or IV amrubicin (control arm) in patients requiring second-line chemotherapy for SCLC refractory or sensitive to first-line platinum-based chemotherapy:
Key Secondary
• Overall survival (OS)
Other Secondary
• Disease control rate (DCR)
• Overall response rate (ORR)
• Duration of response (DR)
• Time to treatment failure (TTF)
• Safety and tolerability |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has provided written informed consent.
2. Is ≥18 years of age for patients enrolled in Europe.
3. Has definitive histologically or cytologically confirmed SCLC (limited or extensive disease).
4. Has progressed or had recurrence within 30 days prior to randomization. This progression or recurrence has to be based on imaging after first-line platinum-based chemotherapy.
5. Has at least one measurable lesion, as defined by RECIST criteria, version 1.1 (see Section 9.2 of Protocol).
6. Has ECOG performance status of 0, 1 or 2 in the Baseline period and at the time of randomization.
7. Is able to take medications orally (ie, no feeding tube).
8. Has adequate organ function as defined by the following laboratory values obtained within 5 days prior to randomization:
a. Hemoglobin value of ≥9.0 g/dL.
b. WBC count of ≥3000/mm3 (ie, ≥3.0 × 109/L by International Units [IU]).
c. Platelet count ≥100,000/mm3 (IU: ≥100 × 109/L).
d. Total serum bilirubin of ≤1.5 mg/dL (except for Grade 1 hyperbilirubinemia due solely to a medical diagnosis of Gilbert’s syndrome).
e. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤5 × ULN.
f. Serum creatinine of ≤1.5 mg/dL.
g. Creatinine clearance of ≥20 mL/min (determined according to institutional standard of care).
9. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to randomization. Male and female patients who have the potential to reproduce must agree to use a highly effective method of birth control (ie, pregnancy rate of less than 1%
per year) during the study and for 6 months after the discontinuation of study medication. Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as implants, injectables, combined oral contraceptives, some intrauterine
devices (IUDs), sexual abstinence, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy.
10. Is willing and able to comply with scheduled visits and study procedures. |
|
| E.4 | Principal exclusion criteria |
1. Has cerebral metastases unless all of the following apply:
a. Cerebral metastases have been treated and controlled, eg, via surgery and/or radiotherapy;
b. Cerebral metastases have been stable for at least 2 months post-intervention; and
c. Patient is not receiving corticosteroids as part of treatment for cerebral metastases.
2. Has a serious illness or serious medical condition(s) including, but not limited to the following:
a. Other concurrently active malignancies excluding malignancies that are in remission for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment.
b. Active systemic infection (ie, body temperature ≥38°C due to infection).
c. Ascites, pleural effusion or pericardial fluid requiring more than one drainage in last 4 weeks.
d. Intestinal obstruction, pulmonary fibrosis, interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder.
e. Uncontrolled diabetes.
f. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV).
g. Gastrointestinal hemorrhage.
h. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C.
i. Patients with autoimmune disorders or history of organ transplantation who require immunosuppressive therapy.
j. Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results.
3. Has had treatment with any of the following within the specified time frame prior to study drug administration:
a. Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to study drug administration).
b. Any anticancer therapy within prior 3 weeks.
c. Extended field radiation within prior 4 weeks or limited field radiation within prior 2 weeks.
d. Any investigational agent received within prior 4 weeks.
4. Has received TAS-102.
5. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).
6. Is a pregnant or lactating female.
7. Is inappropriate for entry into this study in the judgment of the Investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the study.
Tumor assessments will be performed throughout the study based on Response Evaluation Criteria in Solid Tumors (RECIST) as described in the Protocol. Computed tomography (CT) scans of chest/liver/adrenal glands (and magnetic resonance imaging [MRI] of the head in case of cerebral metastases detected via MRI at baseline) will be performed at Baseline and every 6 weeks from the start of study treatment (Day 1, Cycle 1) |
|
| E.5.2 | Secondary end point(s) |
• Overall survival (OS)
• Disease control rate (DCR)
• Overall response rate (ORR)
• Duration of response (DR)
• Time to treatment failure (TTF)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the study.
Tumor assessments will be performed throughout the study based on Response Evaluation Criteria in Solid Tumors (RECIST) as described in the Protocol. Computed tomography (CT) scans of chest/liver/adrenal glands (and magnetic resonance imaging [MRI] of the head in case of cerebral metastases detected via MRI at baseline) will be performed at Baseline and every 6 weeks from the start of study treatment (Day 1, Cycle 1) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| 12 months after the first dose of study medication for the last patient randomized, or until the target number of death events is reached, whichever occurs last. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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