Back to results

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

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

Nintedanib

Docetaxel

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

1199.90.81001 Boehringer Ingelheim Investigational Site
1199.90.81003 Boehringer Ingelheim Investigational Site
1199.90.81007 Boehringer Ingelheim Investigational Site
1199.90.81006 Boehringer Ingelheim Investigational Site
1199.90.81004 Boehringer Ingelheim Investigational Site
1199.90.81002 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nintedanib plus Docetaxel

Arm Description

patients to receive backbone chemotherapy and nintedanib

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Maximum Measured Concentration (Cmax) of Nintedanib

This outcome measure presents the maximum measured concentration (Cmax) of nintedanib in plasma in cycle 1.

Cmax of Docetaxel

This outcome measure presents the Cmax of docetaxel in plasma in cycles 1 and 2.

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.

AUC0-tz of Docetaxel

This outcome measure presents AUC0-tz of docetaxel in plasma in cycles 1 and 2.

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.

AUC0-infinity of Docetaxel

This outcome measure presents the AUC0-infinity of docetaxel in plasma in cycles 1 and 2.

Full Information

NCT ID

NCT02300298

First Posted

November 24, 2014

Last Updated

October 4, 2018

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT02300298

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

December 24, 2014 (Actual)

Primary Completion Date

January 15, 2016 (Actual)

Study Completion Date

October 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Non-Small-Cell Lung

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nintedanib plus Docetaxel

Arm Type

Experimental

Arm Description

patients to receive backbone chemotherapy and nintedanib

Intervention Type

Drug

Intervention Name(s)

Nintedanib

Intervention Description

Nintedanib

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Docetaxel

Primary Outcome Measure Information:

Title

Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1

Description

Time Frame

Cycle 1, from first administration of study medication up to 21 days thereafter.

Secondary Outcome Measure Information:

Title

Maximum Measured Concentration (Cmax) of Nintedanib

Description

This outcome measure presents the maximum measured concentration (Cmax) of nintedanib in plasma in cycle 1.

Time Frame

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.

Title

Cmax of Docetaxel

Description

This outcome measure presents the Cmax of docetaxel in plasma in cycles 1 and 2.

Time Frame

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)

Title

Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 to Time of the Last Quantifiable Concentration (AUC0-tz)

Description

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.

Time Frame

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.

Title

AUC0-tz of Docetaxel

Description

This outcome measure presents AUC0-tz of docetaxel in plasma in cycles 1 and 2.

Time Frame

Title

Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)

Description

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.

Time Frame

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.

Title

AUC0-infinity of Docetaxel

Description

This outcome measure presents the AUC0-infinity of docetaxel in plasma in cycles 1 and 2.

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1199.90.81001 Boehringer Ingelheim Investigational Site

City

Chiba , Kashiwa

Country

Japan

Facility Name

1199.90.81003 Boehringer Ingelheim Investigational Site

City

Kanagawa, Yokohama

Country

Japan

Facility Name

1199.90.81007 Boehringer Ingelheim Investigational Site

City

Osaka, Osakasayama

Country

Japan

Facility Name

1199.90.81006 Boehringer Ingelheim Investigational Site

City

Osaka, Osaka

Country

Japan

Facility Name

1199.90.81004 Boehringer Ingelheim Investigational Site

City

Shizuoka, Sunto-gun

Country

Japan

Facility Name

1199.90.81002 Boehringer Ingelheim Investigational Site

City

Tokyo, Chuo

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

30073583

Citation

Yamamoto N, Kenmotsu H, Goto K, Takeda K, Kato T, Takeda M, Horinouchi H, Saito I, Sarashina A, Tanaka T, Morsli N, Nakagawa K. An open-label feasibility study of nintedanib combined with docetaxel in Japanese patients with locally advanced or metastatic lung adenocarcinoma after failure of first-line chemotherapy. Cancer Chemother Pharmacol. 2018 Oct;82(4):685-694. doi: 10.1007/s00280-018-3649-x. Epub 2018 Aug 3.

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com

Description

Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs