Clinical Trials List
Protocol Number1199.128
NCT Number(ClinicalTrials.gov Identfier)NCT02231164
2015-01-01 - 2018-12-31
Phase III
Terminated6
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
Multicentre, randomised, double-blind, Phase III trial to investigate the efficacy and safety of oral nintedanib plus docetaxel therapy compared to placebo plus docetaxel therapy in patients with stage IIIB/IV or recurrent, adenocarcinoma subtype non-small cell lung cancer after failure of first line chemotherapy
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
Boehringer Ingelheim Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chia-Cheng Tseng Division of Thoracic Medicine
- 王逸熙 Division of Thoracic Medicine
- CHIN-CHOU WANG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shih-Hong Li Division of Hematology & Oncology
- 林倡葦 Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- 黃世豪 Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- 李忠恕 Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- Chien-Ying Liu Division of Hematology & Oncology
- 邱立忠 Division of Hematology & Oncology
- Fu-Tsai Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yu-Chao Lin Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chong-Jen Yu Division of Hematology & Oncology
- 廖為昱 Division of Hematology & Oncology
- 林育齡 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
stage IIIB/IV or recurrent, adenocarcinoma subtype non-small cell lung cancer
Objectives
The primary objective of this study is to evaluate whether treatment with nintedanib in
combination with docetaxel is more effective than treatment with placebo in
combination with docetaxel, as assessed by progression-free survival (PFS) and
overall survival (OS), in patients with locally advanced or metastatic adenocarcinoma
of the lung [stage IIIB or IV Non Small Cell Lung Cell (NSCLC)], who have
progressed after first line platinum- based chemotherapy.
Secondary objectives are to evaluate the objective tumour response rate, the disease
control rate, and to obtain information on quality of life (QOL) of patients.
Test Drug
Nintedanib
Active Ingredient
Nintedanib
Dosage Form
capsules
Dosage
100 or 150
Endpoints
Co-primary Endpoints:
Progression free survival (PFS) by central independent review
Overall survival (OS)
Secondary Endpoints:
Objective tumour response by central independent review
Disease control by central independent review
Quality of life (time to deterioration of cough, dyspnea and pain; and the
global health status/QOL summary score).
Progression free survival (PFS) by central independent review
Overall survival (OS)
Secondary Endpoints:
Objective tumour response by central independent review
Disease control by central independent review
Quality of life (time to deterioration of cough, dyspnea and pain; and the
global health status/QOL summary score).
Inclution Criteria
Inclusion criteria
1. Male or female patients of at least 18 years of age
2. Histologically confirmed, adenocarcinoma of the lung, after failure of first line
platinum-based chemotherapy. First line chemotherapy for locally advanced, or
metastatic (stage IIIB or IV NSCLC according to American Joint Committee on
Cancers, Version 7) or recurrent disease may include continuation or switch
maintenance therapy administered in the absence of disease progression. One prior
adjuvant and/or neoadjuvant chemotherapy is permissible.
3. At least one target tumour lesion that has not been irradiated within the past three
months and that can be accurately measured by magnetic resonance imaging (MRI) or
computerized tomography (CT) with a longest diameter of ≥ 10 mm or ≥15 mm in the
short-axis diameter for a lymph node. If there is only one target lesion, and it is a nonlymph node, it should have a longest diameter of ≥15 mm
4. ECOG performance status score (0 or 1)
5. Signed and dated written informed consent in accordance with ICH-GCP guidelines
and the local legislation
1. Male or female patients of at least 18 years of age
2. Histologically confirmed, adenocarcinoma of the lung, after failure of first line
platinum-based chemotherapy. First line chemotherapy for locally advanced, or
metastatic (stage IIIB or IV NSCLC according to American Joint Committee on
Cancers, Version 7) or recurrent disease may include continuation or switch
maintenance therapy administered in the absence of disease progression. One prior
adjuvant and/or neoadjuvant chemotherapy is permissible.
3. At least one target tumour lesion that has not been irradiated within the past three
months and that can be accurately measured by magnetic resonance imaging (MRI) or
computerized tomography (CT) with a longest diameter of ≥ 10 mm or ≥15 mm in the
short-axis diameter for a lymph node. If there is only one target lesion, and it is a nonlymph node, it should have a longest diameter of ≥15 mm
4. ECOG performance status score (0 or 1)
5. Signed and dated written informed consent in accordance with ICH-GCP guidelines
and the local legislation
Exclusion Criteria
Exclusion criteria
1. More than one prior line of chemotherapy (i.e., 2
nd or 3rd line chemotherapy) for
advanced and/or metastatic (stage III B or IV NSCLC) or recurrent disease
2. Patients known to be positive for activating Epidermal Growth Factor Receptor
(EGFR) mutation; if the EGFR mutational status is not known, then the patients will
be tested using archived or fresh biopsied tumour, and if positive will be excluded
3. Patients known to be positive for ALK translocation; if the ALK translocation status
is not known, then the patients will be tested using archived or fresh biopsied tumour,
and if positive will be excluded
4. Non-permissible treatments:
a. Previous therapy with other VEGF or VEGFR inhibitors (other than
bevacizumab) or docetaxel for the treatment of NSCLC at any time
b. Prior monotherapy with an EGFR inhibitor except as maintenance therapy
5. Non-permissible treatments within 4 weeks prior to start of study therapy:
a. Other investigational drugs
b. Chemo-, hormone-, radiotherapy (except for radiotherapy to extremities) or
immunotherapy or therapy with monoclonal antibodies or small tyrosine
kinase inhibitors
6. Radiotherapy (except extremities and brain) within the past three months prior to
baseline imaging
7. Persistence of clinically relevant therapy related toxicities from previous
chemotherapy and/or radiotherapy (AE from previous treatment ≥ Grade 2)
8. Laboratory values outside the following ranges:
a. Serum creatinine > 1.5 times the upper limit of normal (ULN)
b. Proteinuria CTCAE grade 2 or greater
c. Total bilirubin above the upper limit of normal
d. ALT or AST > 1.5 x ULN
e. Prothrombin time and/or partial thromboplastin time greater than 50 %
deviation from normal limits
f. International normalised ratio ( INR) > 3
g. Absolute neutrophil count (ANC) < 1500/mm3
h. Platelets < 100000/ mm3
i. Haemoglobin < 9.0 g/dL
9. Any of the following conditions:
a. Pre-existing ascites and/or clinically significant pleural effusion
b. Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in
the present trial
c. Current peripheral neuropathy CTCAE grade 2 except due to trauma
d. Major injuries and/or surgery within the past ten days prior to randomisation
with incomplete wound healing
e. Decompensated diabetes mellitus or other contraindication to high dose
corticosteroid therapy
f. Active or chronic hepatitis C and/or B infection
g. Serious illness or concomitant non-oncological disease such as neurologic-,
psychiatric active alcohol or drug abuse, infectious disease or active ulcers
(gastro-intestinal malabsorption or other conditions, skin), history of holloworgan perforations or laboratory abnormality that may increase the risk
associated with study participation or study drug administration and in the
judgment of the investigator would make the patient inappropriate for entry
into the study
h. Other malignancy within the past three years other than basal cell skin cancer,
or carcinoma in situ of the cervix
i. Active brain metastases or leptomeningeal disease stable for < 4 weeks (e.g.,
no previous adequate treatment with radiotherapy, symptomatic, requiring
treatment with anti-convulsants). If brain metastases have been treated, they
must be stable for ≥4 weeks. Dexamethasone therapy will be allowed if
administered at a stable dose for at least four weeks prior to randomisation.
Patients with newly diagnosed brain metastases will be excluded from the
study until/unless treated as described above
j. Radiographic evidence (CT or MRI) of cavitary or necrotic tumours or
centrally located tumours with local invasion of major blood vessels
k. History of clinically significant haemoptysis within the past 3 months (more
than one teaspoon of fresh blood per day)
l. Bleeding or thrombotic disorders requiring anticoagulant therapy such as
warfarin, or similar agents requiring therapeutic INR monitoring (treatment
with low molecular weight heparin and/or heparin flush as needed for
maintenance of an indwelling intravenous device is allowed) or anti-platelet
therapy (except for chronic low-dose therapy with acetylsalicylic acid ≤ 325
mg per day)
m. History of major thrombotic event or known inherited predisposition to
thrombosis, or clinically relevant major bleeding event in the past 6 months
n. Significant cardiovascular diseases (i.e. hypertension not controlled by
medical therapy, unstable angina, history of myocardial infarction within the
past 6 months, congestive heart failure > NYHA II, serious cardiac
arrhythmia, pericardial effusion
10. Patients of childbearing potential who are sexually active and unwilling to use a
highly effective method of contraception (e.g. contraceptive implants, injectables,
combined oral contraceptives, some intrauterine devices or vasectomized partner for
participating females, a double barrier method such as condom plus diaphragm with
spermicide for participating males) during the trial and for at least 3 months after the
end of the treatment with nintedanib and for at least 6 months after the end of the
therapy with docetaxel. Patients will be considered to be of childbearing potential
unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy,
or post-menopausal for at least 1 year
11. Pregnancy or breast feeding
12. Any contraindications for therapy with docetaxel or history of severe hypersensitivity
reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80).
Hypersensitivity to nintedanib and/or the excipients of the trial drugs.
Hypersensitivity to contrast media
13. Patients unable to comply with the study protocol and follow-up schedule, for any
reason
1. More than one prior line of chemotherapy (i.e., 2
nd or 3rd line chemotherapy) for
advanced and/or metastatic (stage III B or IV NSCLC) or recurrent disease
2. Patients known to be positive for activating Epidermal Growth Factor Receptor
(EGFR) mutation; if the EGFR mutational status is not known, then the patients will
be tested using archived or fresh biopsied tumour, and if positive will be excluded
3. Patients known to be positive for ALK translocation; if the ALK translocation status
is not known, then the patients will be tested using archived or fresh biopsied tumour,
and if positive will be excluded
4. Non-permissible treatments:
a. Previous therapy with other VEGF or VEGFR inhibitors (other than
bevacizumab) or docetaxel for the treatment of NSCLC at any time
b. Prior monotherapy with an EGFR inhibitor except as maintenance therapy
5. Non-permissible treatments within 4 weeks prior to start of study therapy:
a. Other investigational drugs
b. Chemo-, hormone-, radiotherapy (except for radiotherapy to extremities) or
immunotherapy or therapy with monoclonal antibodies or small tyrosine
kinase inhibitors
6. Radiotherapy (except extremities and brain) within the past three months prior to
baseline imaging
7. Persistence of clinically relevant therapy related toxicities from previous
chemotherapy and/or radiotherapy (AE from previous treatment ≥ Grade 2)
8. Laboratory values outside the following ranges:
a. Serum creatinine > 1.5 times the upper limit of normal (ULN)
b. Proteinuria CTCAE grade 2 or greater
c. Total bilirubin above the upper limit of normal
d. ALT or AST > 1.5 x ULN
e. Prothrombin time and/or partial thromboplastin time greater than 50 %
deviation from normal limits
f. International normalised ratio ( INR) > 3
g. Absolute neutrophil count (ANC) < 1500/mm3
h. Platelets < 100000/ mm3
i. Haemoglobin < 9.0 g/dL
9. Any of the following conditions:
a. Pre-existing ascites and/or clinically significant pleural effusion
b. Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in
the present trial
c. Current peripheral neuropathy CTCAE grade 2 except due to trauma
d. Major injuries and/or surgery within the past ten days prior to randomisation
with incomplete wound healing
e. Decompensated diabetes mellitus or other contraindication to high dose
corticosteroid therapy
f. Active or chronic hepatitis C and/or B infection
g. Serious illness or concomitant non-oncological disease such as neurologic-,
psychiatric active alcohol or drug abuse, infectious disease or active ulcers
(gastro-intestinal malabsorption or other conditions, skin), history of holloworgan perforations or laboratory abnormality that may increase the risk
associated with study participation or study drug administration and in the
judgment of the investigator would make the patient inappropriate for entry
into the study
h. Other malignancy within the past three years other than basal cell skin cancer,
or carcinoma in situ of the cervix
i. Active brain metastases or leptomeningeal disease stable for < 4 weeks (e.g.,
no previous adequate treatment with radiotherapy, symptomatic, requiring
treatment with anti-convulsants). If brain metastases have been treated, they
must be stable for ≥4 weeks. Dexamethasone therapy will be allowed if
administered at a stable dose for at least four weeks prior to randomisation.
Patients with newly diagnosed brain metastases will be excluded from the
study until/unless treated as described above
j. Radiographic evidence (CT or MRI) of cavitary or necrotic tumours or
centrally located tumours with local invasion of major blood vessels
k. History of clinically significant haemoptysis within the past 3 months (more
than one teaspoon of fresh blood per day)
l. Bleeding or thrombotic disorders requiring anticoagulant therapy such as
warfarin, or similar agents requiring therapeutic INR monitoring (treatment
with low molecular weight heparin and/or heparin flush as needed for
maintenance of an indwelling intravenous device is allowed) or anti-platelet
therapy (except for chronic low-dose therapy with acetylsalicylic acid ≤ 325
mg per day)
m. History of major thrombotic event or known inherited predisposition to
thrombosis, or clinically relevant major bleeding event in the past 6 months
n. Significant cardiovascular diseases (i.e. hypertension not controlled by
medical therapy, unstable angina, history of myocardial infarction within the
past 6 months, congestive heart failure > NYHA II, serious cardiac
arrhythmia, pericardial effusion
10. Patients of childbearing potential who are sexually active and unwilling to use a
highly effective method of contraception (e.g. contraceptive implants, injectables,
combined oral contraceptives, some intrauterine devices or vasectomized partner for
participating females, a double barrier method such as condom plus diaphragm with
spermicide for participating males) during the trial and for at least 3 months after the
end of the treatment with nintedanib and for at least 6 months after the end of the
therapy with docetaxel. Patients will be considered to be of childbearing potential
unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy,
or post-menopausal for at least 1 year
11. Pregnancy or breast feeding
12. Any contraindications for therapy with docetaxel or history of severe hypersensitivity
reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80).
Hypersensitivity to nintedanib and/or the excipients of the trial drugs.
Hypersensitivity to contrast media
13. Patients unable to comply with the study protocol and follow-up schedule, for any
reason
The Estimated Number of Participants
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Taiwan
27 participants
-
Global
800 participants
