Nintedanib Plus Docetaxel in Japanese Patients With Adenocarcinoma Subtype Non-small Cell Lung Cancer After Failure of First Line Chemotherapy

Study Overview
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Brief Summary
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To determine the appropriateness of the dose of nintedanib 200 mg b.i.d. plus docetaxel 75 mg/m2 as starting dose by evaluating the safety in Japanese patients with body surface area (BSA) <1.5 m2 and locally advanced or metastatic adenocarcinoma subtype non-small cell lung cancer (NSCLC) after failure of first line platinum- based chemotherapy

Official Title
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An Open Label Phase I Safety run-in Trial of Oral Nintedanib Plus Docetaxel Therapy in Japanese Patients With Locally Advanced or Metastatic Adenocarcinoma Subtype Non-small Cell Lung Cancer After Failure of Platinum-based First Line Chemotherapy

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients aged 20 years or older at the date of informed consent Patients with body surface area (BSA)<1.5 m2 at screening Patients with histologically/cytologically confirmed locally advanced or metastatic adenocarcinoma subtype non-small cell lung cancer (NSCLC) after failure of first line platinum-based chemotherapy (patients with non-target lesion only are eligible) First line chemotherapy may include continuation or switch maintenance therapy. One prior adjuvant and/or neoadjuvant chemotherapy is accepted. Patients who have life expectancy of at least 3 months Patients who are Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening Patients obtained written informed consent in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP)and Japanese GCP Exclusion criteria: Patients who have received more than one prior line of chemotherapy (i.e., second or third line chemotherapy) for advanced or metastatic NSCLC (Prior monotherapies with an epidermal growth factor receptor tyrosine kinase inhibitors [EGFR-TKI]) or anaplastic lymphoma kinase (ALK) inhibitor can be allowed) Patients who have received previous therapy with other vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) inhibitors (other than bevacizumab) for the treatment of NSCLC at any time Patients who have received following treatments within 4 weeks prior to start of study therapy 1) Other investigational drugs 2) Chemo-, hormone-, immunotherapy, or monoclonal antibody. Patients who have received molecular target therapy including EGFR TKIs and ALK inhibitors within 2 weeks prior to start of study therapy Patents who have received radiotherapy within the past 3 months (in the case of limited -field [e.g. brain or bone metastasis] radiotherapy with palliative intent), within 2 weeks) prior to start of study therapy Patients who not recovered clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy (=CTCAE grade 2 Adverse Event from previous treatment) at screening further exclusion criteria may be applied

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nintedanib plus Docetaxel<br>patients to receive backbone chemotherapy and nintedanib | Drug: Nintedanib<br>* Nintedanib<br>Drug: Docetaxel<br>* Docetaxel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1 | DLT was defined as any of the following study drug related adverse events (AEs): Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 non-haematological toxicity except transient electrolyte abnormality and isolated increase of gamma-glutamyltransferase (GGT); gastrointestinal toxicity, despite adequate supportive care CTCAE grade 4 haematological toxicity; Neutrophil count decreased or white blood cell count (not associated with fever) for >7 days despite adequate supportive treatment CTCAE grade 4 febrile neutropenia with fever ≥38.5 degrees CTCAE grade ≥2 alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) increase in conjunction with CTCAE grade ≥2 total bilirubin increase Inability to resume nintedanib dosing within 14 days after stopping Investigators judged clinically as DLT after dose reduction and severity medically notable (CTCAE, version 3). Sponsor with safety review committee was allowed to confirm the adequacy of this judgment. | Cycle 1, from first administration of study medication up to 21 days thereafter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Measured Concentration (Cmax) of Nintedanib | This outcome measure presents the maximum measured concentration (Cmax) of nintedanib in plasma in cycle 1. | At 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 h after first drug administration of docetaxel in cycle 1. | 
| Cmax of Docetaxel | This outcome measure presents the Cmax of docetaxel in plasma in cycles 1 and 2. | just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered) | 
| Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 to Time of the Last Quantifiable Concentration (AUC0-tz) | This outcome measure presents the area under the concentration-time curve of nintedanib over the time interval from 0 to time of the last quantifiable concentration in plasma (AUC0-tz) in cycle 1. | At 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 after first drug administration of docetaxel in cycle 1. | 
| AUC0-tz of Docetaxel | This outcome measure presents AUC0-tz of docetaxel in plasma in cycles 1 and 2. | just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered) | 
| Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | This outcome measure presents the Area under the concentration-time curve of nintedanib over the time interval from 0 extrapolated to infinity in plasma (AUC0-infinity) in cycle 1. | at 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 h after first drug administration of docetaxel in cycle 1. | 
| AUC0-infinity of Docetaxel | This outcome measure presents the AUC0-infinity of docetaxel in plasma in cycles 1 and 2. | just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered) |