NCT02300298

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

Completed Phase 1 Results posted Last updated 11 February 2025

What this trial tests

Phase 1 trial testing Nintedanib in Carcinoma, Non-Small-Cell Lung in 10 participants. Completed in 27 October 2017.

Timeline

24 December 2014

Primary endpoint
15 January 2016

27 October 2017

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	24 December 2014
Primary completion	15 January 2016
Estimated completion	27 October 2017
Sites	6 locations across Japan

Drugs / interventions tested

• Nintedanib (NINTEDANIB) — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Carcinoma, Non-Small-Cell Lung — all drugs for Carcinoma, Non-Small-Cell Lung →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

20 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1 Primary · Cycle 1, from first administration of study medication up to 21 days thereafter.

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 amino

Total with DLTs - all grades

Group	Value	95% CI
Nintedanib Plus Docetaxel	2

Total with DLTs - grade 1/2

Group	Value	95% CI
Nintedanib Plus Docetaxel	0

Total with DLTs - grade 3/4/5

Group	Value	95% CI
Nintedanib Plus Docetaxel	2

Hepatobiliary disorders (hep. dis.) - all grades

Group	Value	95% CI
Nintedanib Plus Docetaxel	1

Hep. dis. - grade 1/2

Group	Value	95% CI
Nintedanib Plus Docetaxel	1

Hep. dis. - grade 3/4/5

Group	Value	95% CI
Nintedanib Plus Docetaxel	0

Hep. dis. - hyperbilirubinaemia - all grades

Group	Value	95% CI
Nintedanib Plus Docetaxel	1

Hep. dis. - hyperbilirubinaemia - grade 1/2

Group	Value	95% CI
Nintedanib Plus Docetaxel	1

Maximum Measured Concentration (Cmax) of Nintedanib Secondary · 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.

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

Group	Value	95% CI
Nintedanib Plus Docetaxel	65.1	± 86.6

Cmax of Docetaxel Secondary · 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)

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

Cycle 1

Group	Value	95% CI
Nintedanib Plus Docetaxel	2710	± 37.6

Cycle 2

Group	Value	95% CI
Nintedanib Plus Docetaxel	2680	± 49.6

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

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.

Group	Value	95% CI
Nintedanib Plus Docetaxel	342	± 59.8

AUC0-tz of Docetaxel Secondary · 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)

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

Cycle 1

Group	Value	95% CI
Nintedanib Plus Docetaxel	3080	± 27.4

Cycle 2

Group	Value	95% CI
Nintedanib Plus Docetaxel	3320	± 29.8

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

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.

Group	Value	95% CI
Nintedanib Plus Docetaxel	381	± 62.7

AUC0-infinity of Docetaxel Secondary · 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)

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

Cycle 1

Group	Value	95% CI
Nintedanib Plus Docetaxel	3320	± 26.2

Cycle 2

Group	Value	95% CI
Nintedanib Plus Docetaxel	3590	± 26.6

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first administration of docetaxel up to 28 days after the day of the last administration of study medication (docetaxel and/or nintedanib) up to 1002 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nintedanib Plus Docetaxel

Serious: 6/10 (60%)

Deaths: 0/10

Serious adverse events (5 terms)

Reaction	System	Nintedanib Plus Docetaxel
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Fatigue	General disorders	—
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Paraneoplastic pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—

Other adverse events (68 terms — click to expand)

Reaction	System	Nintedanib Plus Docetaxel
Neutrophil count decreased	Investigations	—
White blood cell count decreased	Investigations	—
Alopecia	Skin and subcutaneous tissue disorders	—
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Constipation	Gastrointestinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Fatigue	General disorders	—
Gamma-glutamyltransferase increased	Investigations	—
Decreased appetite	Metabolism and nutrition disorders	—
Peripheral sensory neuropathy	Nervous system disorders	—
Hypoaesthesia	Nervous system disorders	—
Oedema peripheral	General disorders	—
Pyrexia	General disorders	—
Dysgeusia	Nervous system disorders	—
Insomnia	Psychiatric disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Lacrimation increased	Eye disorders	—
Ocular hyperaemia	Eye disorders	—
Vomiting	Gastrointestinal disorders	—
Malaise	General disorders	—
Cystitis	Infections and infestations	—
Upper respiratory tract infection	Infections and infestations	—
Blood alkaline phosphatase increased	Investigations	—
Haemoglobin decreased	Investigations	—
Lymphocyte count decreased	Investigations	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Headache	Nervous system disorders	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Flushing	Vascular disorders	—
Dry eye	Eye disorders	—
Eyelid ptosis	Eye disorders	—
Oral pain	Gastrointestinal disorders	—
Proctalgia	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Face oedema	General disorders	—
Medical device site pain	General disorders	—

Most-reported serious reactions: Metastases to central nervous system, Fatigue, Metastases to meninges, Paraneoplastic pleural effusion, Cancer pain.

Data from ClinicalTrials.gov NCT02300298 adverse events section.

Sponsor's own description

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

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment.
   Liu G, Chen T, Ding Z, Wang Y, et al · · 2021 · cited 131× · PMID 33655556 · DOI 10.1111/cpr.13009
2. Efficacy and safety of nintedanib in patients with non-small cell lung cancer, and novel insights in radiation-induced lung toxicity.
   Yan S, Xue S, Wang T, Gao R, et al · · 2023 · cited 10× · PMID 37637045 · DOI 10.3389/fonc.2023.1086214
3. Clinical development of nintedanib for advanced non-small-cell lung cancer.
   Takeda M, Okamoto I, Nakagawa K. · · 2015 · cited 10× · PMID 26622180 · DOI 10.2147/tcrm.s76646
4. 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.
   Yamamoto N, Kenmotsu H, Goto K, Takeda K, et al · · 2018 · cited 3× · PMID 30073583 · DOI 10.1007/s00280-018-3649-x