Clinical trial NCT02300298: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-11-25
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1
timeFrame: Cycle 1, from first administration of study medication up to 21 days thereafter.
Secondary outcomes:
measure: Maximum Measured Concentration (Cmax) of Nintedanib
timeFrame: 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.
measure: Cmax of Docetaxel
timeFrame: 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)
measure: Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 to Time of the Last Quantifiable Concentration (AUC0-tz)
timeFrame: 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.
measure: AUC0-tz of Docetaxel
timeFrame: 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)
measure: Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
timeFrame: 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.
measure: AUC0-infinity of Docetaxel
timeFrame: 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)
Other outcomes:
Locations:
city: Chiba , Kashiwa
country: Japan
facility: 1199.90.81001 Boehringer Ingelheim Investigational Site
city: Kanagawa, Yokohama
country: Japan
facility: 1199.90.81003 Boehringer Ingelheim Investigational Site
city: Osaka, Osakasayama
country: Japan
facility: 1199.90.81007 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1199.90.81006 Boehringer Ingelheim Investigational Site
city: Shizuoka, Sunto-gun
country: Japan
facility: 1199.90.81004 Boehringer Ingelheim Investigational Site
city: Tokyo, Chuo
country: Japan
facility: 1199.90.81002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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.