Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009-010432-18 | EudraCT Number | EudraCT |
Not provided
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The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.
The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.
Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIBW 2992 + Sirolimus | Experimental | Dose escalation of the combination BIBW 2992 plus Sirolimus. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIBW 2992 | Drug | Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Dose Limiting Toxicities (DLT) | Number of participants with of dose limiting toxicities (DLT) | 2 first cycles, 56 days |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response | Best overall response (unconfirmed) according to RECIST v1.1 | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Objective Response |
Not provided
Inclusion criteria:
Pathologically or cytologically confirmed diagnosis of Stage IIIB or Stage IV NSCLC
Patients who have failed conventional treatment (at least 1 prior treatment line), or for whom no therapy of proven efficacy exists
Patients whose tumors:
Patients aged 18 years or older
Life expectancy of at least three (3) months
Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0-2
Written informed consent that is consistent with ICH-GCP guidelines
Exclusion criteria:
Prior major surgery, chemotherapy or radiation therapy within 4 weeks before start of therapy.
Prior treatment with an mTOR inhibitor within the past 4 weeks before start of therapy or concomitantly with this study
Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of run-in treatment with Sirolimus
Active CNS metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids)
Severe alteration in serum fasting cholesterol (equal or more than 350 mg/dL) or triglycerides (equal or more than 400 mg/dL). Patients may be allowed to enrol on the trial after initiation of lipid lowering agents.
Requirement for treatment with any of the prohibited concomitant medications:
Any contraindications for therapy with Sirolimus.
Known hypersensitivity to BIBW 2992, Sirolimus or other rapamycin analogues (everolimus, temsirolimus, deforolimus, etc.) or the excipients of any of the trial drugs.
Use of any investigational drug within 4 weeks before start of therapy.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.70.34001 Boehringer Ingelheim Investigational Site | Badalona (Barcelona) | Spain | ||||
| 1200.70.34008 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28625629 | Derived | Moran T, Palmero R, Provencio M, Insa A, Majem M, Reguart N, Bosch-Barrera J, Isla D, Costa EC, Lee C, Puig M, Kraemer S, Schnell D, Rosell R. A phase Ib trial of continuous once-daily oral afatinib plus sirolimus in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer and/or disease progression following prior erlotinib or gefitinib. Lung Cancer. 2017 Jun;108:154-160. doi: 10.1016/j.lungcan.2017.03.009. Epub 2017 Mar 22. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Afa30+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily. |
| FG001 | Afa30+Sir03 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Run-in Period (8 Days) |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Sirolimus (rapamycin) | Drug | Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs. |
|
Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1
| From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Rate of Disease Control | Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1 | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA. | Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA. This endpoint was not analysed in the study report as the available data was too limited. | Multiple time points during the trial |
| Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss) | Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss) | 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib |
| AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss) | Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib. | 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib |
| Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss) | Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss) | 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib |
| AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss) | Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib. | 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib |
| Occurrence of Adverse Events According to CTCAE, Version 3.0 | Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0 | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Percentage of Patients With Drug-related AEs | Percentage of patients with drug-related adverse events (AEs). | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin | Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases. | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| Barcelona |
| Spain |
| 1200.70.34009 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1200.70.34006 Boehringer Ingelheim Investigational Site | Girona | Spain |
| 1200.70.34007 Boehringer Ingelheim Investigational Site | L'Hospitalet de Llobregat (Barcelona) | Spain |
| 1200.70.34005 Boehringer Ingelheim Investigational Site | Majadahonda (Madrid) | Spain |
| 1200.70.34004 Boehringer Ingelheim Investigational Site | Valencia | Spain |
| 1200.70.34002 Boehringer Ingelheim Investigational Site | Zaragoza | Spain |
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily.
| FG002 | Afa30+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily. |
| FG003 | Afa30+Sir10 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| FG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| FG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Discontinued Before Starting Course 3 |
|
|
| Discontinued After Starting Course 3 |
|
|
Treated set which included all patients who recieved at least one dose of the trial drug during the first and second treatment counrses.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Afa30+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily. |
| BG001 | Afa30+Sir03 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily. |
| BG002 | Afa30+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily. |
| BG003 | Afa30+Sir10 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| BG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| BG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Occurrence of Dose Limiting Toxicities (DLT) | Number of participants with of dose limiting toxicities (DLT) | Treated set | Posted | Number | Participants | 2 first cycles, 56 days |
|
|
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Best Overall Response | Best overall response (unconfirmed) according to RECIST v1.1 | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Objective Response | Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1 | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate of Disease Control | Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1 | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA. | Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA. This endpoint was not analysed in the study report as the available data was too limited. | Treated set. This endpoint was not analysed in the study report as the available data was too limited. | Posted | Multiple time points during the trial |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss) | Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss) | Pharmacokinetic (PK) set which included all patients in the treated set who had taken at least 1 dose of study medication and for whom at least 1 valid blood or plasma concentration was available. No patients in the Afa40+Sir05 group had analyzable data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss) | Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib. | Pharmacokinetic (PK) set which included all patients in the treated set who had taken at least 1 dose of study medication and for whom at least 1 valid blood or plasma concentration was available. No patients in the Afa40+Sir05 group had analyzable data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss) | Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss) | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss) | Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Occurrence of Adverse Events According to CTCAE, Version 3.0 | Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0 | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Patients With Drug-related AEs | Percentage of patients with drug-related adverse events (AEs). | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin | Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases. | Treated set | Posted | Number | Percentage of participants | From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days |
|
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afa30+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily. | 4 | 12 | 12 | 12 | ||
| EG001 | Afa30+Sir03 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily. | 6 | 9 | 9 | 9 | ||
| EG002 | Afa30+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily. | 7 | 9 | 8 | 9 | ||
| EG003 | Afa30+Sir10 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. | 2 | 3 | 3 | 3 | ||
| EG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. | 1 | 3 | 3 | 3 | ||
| EG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.0 | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Neurological decompensation | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Neutrophilia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Ocular icterus | Eye disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Trichomegaly | Eye disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cheilitis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Tooth discolouration | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Facial pain | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Xerosis | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Oral infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Periumbilical abscess | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Ejection fraction abnormal | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Fistula | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.0 | Systematic Assessment |
| |
| Alexia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Bladder spasm | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Leukocyturia | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oliguria | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Vaginal inflammation | Reproductive system and breast disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Respiratory acidosis | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nail dystrophy | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nail toxicity | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Plantar erythema | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Urticaria papular | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077716 | Afatinib |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |
Not provided
Not provided
| Withdrawal by Subject |
|
| Dose Limiting Toxicity (DLT) |
|
| Non compliance with the protocol |
|
| Progressive Disease |
|
| DLT |
|
| Other adverse event |
|
| Male |
|
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily.
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| Afa30+Sir10 |
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
| OG003 | Afa30+Sir10 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| OG003 | Afa30+Sir10 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| Afa30+Sir10 |
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| Afa30+Sir10 |
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|
| Afa30+Sir10 |
Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily. |
| OG004 | Afa40+Sir01 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily. |
| OG005 | Afa40+Sir05 | Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily. |
|
|