| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage IV squamous NSCLC patients who have progressed after platinum-based chemotherapy |
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| E.1.1.1 | Medical condition in easily understood language |
| Patients who have been diagnosed with lung cancer who have received previous chemotherapy |
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| 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 | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10025125 |
| E.1.2 | Term | Lung squamous cell carcinoma stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| 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 |
| Compare treatment with abemaciclib versus docetaxel therapy with respect to investigator-assessed progression-free survival (PFS) in patients with Stage IV squamous cell carcinoma NSCLC who have relapsed after prior platinum-based therapy for advanced disease. |
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| E.2.2 | Secondary objectives of the trial |
•To evaluate the pharmacokinetic parameters including abemaciclib and its active metabolites
•To compare treatment of abemaciclib versus docetaxel with respect to the following:
• Overall survival
• Objective response rate
• Disease control rate
• Time to worsening of Performance Status
• The safety and tolerability using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
• Change from baseline in patient-reported outcomes including: 1) the MD Anderson Symptom Inventory Lung Cancer (MDASI-LC) questionnaire pain and disease-related symptoms scores; and 2) the EuroQol Group’s EQ-5D-5L questionnaire index score, derived from the 5-item descriptive system, and visual analog scale (VAS) self-rated health score.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Have confirmed diagnosis of stage IV NSCLC disease predominantly squamous histology according to the American Joint Committee on Cancer on Cancer Staging Handbook (Edge et al. 2009). Squamous NSCLC diagnosis must be confirmed by histology or cytology local pathology report.
[2] Availability of adequate formalin-fixed paraffin-embedded (FFPE) tumor derived material (tumor blocks or 10 slides minimum) from a core needle biopsy or surgery for analysis of biomarkers. This sample should be the most recent available sample containing adequate material. Re-biopsy after progression from prior therapy is not required.
[3]Have failed first line platinum-based therapy and who have had no more than two prior therapies one of which may be an immune checkpoint inhibitor.Patients with recurrent disease after adjuvant or neoadjuvant therapy or patients who have received combined chemotherapy and radiation for locally advanced disease are eligible, if:
*The patient has progressed within 6 months after completion of adjuvant or neoadjuvant platinum-based therapy (adjuvant therapy will be considered the patient’s one and only prior first-line, platinum-based chemotherapy). The time from completion of the last cycle of adjuvant or neoadjuvant therapy to progression must be less than 6 months. For radiotherapy for locally advanced disease with curative intent with chemotherapy (platinum based therapy), the time of completion of chemotherapy or radiotherapy, whichever finishes last, to progression must be less than 6 months to count as a line of therapy.
•May not have received docetaxel as monotherapy or in combination with platinum therapy in first-line setting, or in the neoadjuvant/adjuvant setting
a. Prior paclitaxel therapy as monotherapy or in combination is permitted in first line, or in neoadjuvant/adjuvant setting
•Prior immunotherapy is allowed and does not count as a line therapy.
[4]Have a performance status (PS) of [0 to 1] on the Eastern Cooperative Oncology Group (ECOG) scale.
[5]Have the presence of measureable disease as defined by the Response Evaluation Criteria In Solid Tumors RECIST 1.1 (Eisenhauer et al. 2009)
[6]Have discontinued all previous treatments for cancer (including chemotherapy, radiotherapy, immunotherapy, and endocrine therapy) for at least 21 days for myelosuppressive agents; or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia
•Radiation therapy: Prior radiotherapy to chest permitted if completed >3 weeks; and prior radiotherapy to the brain is permitted if completed >4 weeks with assessment of stable disease. Patients must have recovered from the acute toxic effects of the treatment prior to the first dose of study treatment.
[7]Have adequate organ function, including:
•hematologic: absolute neutrophil count (ANC) ³1.5 × 109/L, platelets ³100 × 109/L, and hemoglobin ³9 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial study drug treatment must not begin earlier than the day after the erythrocyte transfusion.
•hepatic: bilirubin £1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) £3 times ULN. If significant liver metastasis are known to be present, then AST and ALT can be < 5.0 times ULN.
•renal: Calculated creatinine clearance ≥50 ml/min (per the Cockcroft Gault formula or equivalent and/or 24-hour urine collection.
[8]Are ≥ 18 years of age
[9]Have agreed contraception methods as follows
[9a]Are a man and agree to use a reliable medically approved method of birth control (eg, intrauterine device [IUD], birth control pills, or barrier method) and to not donate sperm during the study and for at least 3 months following the last dose of study drugs(s) or country requirements, whichever is longer]
[9b]Are women of child-bearing potential who test negative for pregnancy within 14 days of start of study treatment and agree to use medically approved method of birth control (eg, intrauterine device [IUD], birth control pills, or barrier method) during the study and for 3 months following the last dose of the study drug(s) or country requirements, whichever is longer
[10]Have an estimated life expectancy of at least 12 weeks and in the judgment of the investigator, will be able to complete at least 2 cycles of treatment |
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| E.4 | Principal exclusion criteria |
[14]Are currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
[15]Have known or suspected allergy to docetaxel or any of its components
[16]Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug of nonmyelosuppressive or myelosuppressive agent, respectively
[17]Have received prior treatment with any CDK4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)
[18]Have had major surgery (excluding biopsy) < 28 days of the initial dose of study drug and/or have not recovered from the acute effects of the surgery
[19]Have a personal history within the last 12 months of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
[20]Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel)
[21]Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
[22]Have the presence of unstable central nervous system (CNS) metastasis:
•History of CNS metastasis or stable CNS metastases are allowed (no longer requiring active therapy such as steroid medications). Patients with symptoms of CNS involvement or a history of CNS metastasis will have brain scan during baseline procedures to document stability. Patients having prior brain scan within 45 days of starting therapy and without symptoms of CNS metastases (stable or unstable) do not need to repeat scan at baseline (within 28 days of starting study treatment).
•Off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery)
•Prior radiotherapy to the brain must be completed >4 weeks prior to randomization with assessment of stable disease.
•Prior surgical resection should be performed at least 28 days prior to randomization. The patient may have no evidence of Grade ≥1 CNS hemorrhage based on pretreatment magnetic resonance imaging (MRI) or intravenous (I.V.) contrast computed tomography (CT) scan (performed within 28 days before starting study treatment).
[23]Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen, or hepatitis C antibodies). Screening is not required for enrollment.
[24]Are female, pregnant and lactating women; unwilling to use medically effective birth control method
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measure is investigator-assessed PFS as defined as the time from randomization until the first evidence of objective progression as defined by RECIST 1.1 (Eisenhauer et al. 2009) or death from any cause, whichever is earlier. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Overall Survival
PK
Objective Response Rate
Disease Control Rate
Time to Worsening ECOG Performance Status
Health Outcomes
|
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every visit
Cycle 1 and Cycle 4
Every visit
Every visit
Every visit
Every visit
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| 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.6.13.1 | Other scope of the trial description |
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| 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 | No |
| 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) | No |
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
| Australia |
| France |
| Germany |
| Hungary |
| Italy |
| Korea, Republic of |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Taiwan |
| Ukraine |
| United States |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 21 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 21 |
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