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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02300298
• Other study ID #: 1199.90
• Status: Completed
• Phase: Phase 1
• Start date: December 24, 2014
• Est. completion date: October 27, 2017

Study information

• Verified date: October 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 27, 2017
• Est. primary completion date: January 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion criteria:

1. Patients aged 20 years or older at the date of informed consent

2. Patients with body surface area (BSA)<1.5 m2 at screening

3. 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.

4. Patients who have life expectancy of at least 3 months

5. Patients who are Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening

6. Patients obtained written informed consent in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP)and Japanese GCP

Exclusion criteria:

1. 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)

2. 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

3. 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.

4. Patients who have received molecular target therapy including EGFR TKIs and ALK inhibitors within 2 weeks prior to start of study therapy

5. 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

6. 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Nintedanib
Nintedanib
• Docetaxel
Docetaxel

Locations

Country	Name	City	State
Japan	1199.90.81001 Boehringer Ingelheim Investigational Site	Chiba , Kashiwa
Japan	1199.90.81003 Boehringer Ingelheim Investigational Site	Kanagawa, Yokohama
Japan	1199.90.81006 Boehringer Ingelheim Investigational Site	Osaka, Osaka
Japan	1199.90.81007 Boehringer Ingelheim Investigational Site	Osaka, Osakasayama
Japan	1199.90.81004 Boehringer Ingelheim Investigational Site	Shizuoka, Sunto-gun
Japan	1199.90.81002 Boehringer Ingelheim Investigational Site	Tokyo, Chuo

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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)
Secondary	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.
Secondary	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)
Secondary	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.
Secondary	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)

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