Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005230-10 | EudraCT Number | EudraCT |
Not provided
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The trial is divided in two parts, Part A and Part B. Part A will involve dose-finding of dose-limiting toxicity (DLT) and MTD in patients with advanced solid tumours. Part B will involve expansion of the MTD to 3 cohorts including non-small cell lung cancer squamous histology, recurrent/ metastatic squamous cell carcinoma of head and neck and other advanced solid tumours (except sarcomas).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| combination arm | Experimental | Patients to receive afatinib once daily plus weekly cetuximab infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab( erbitux®) | Drug | once per week |
| |
| Afatinib |
| Measure | Description | Time Frame |
|---|---|---|
| MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib). | Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD is defined as the highest dose level at which less than 33% of the patients experience DLT in first treatment cycle. | First 21 days treatment cycle |
| Dose Limiting Toxicities During Cycle 1 | Number of Patients With Dose Limiting Toxicity (DLT) Occurring during Cycle 1. The following drug related AEs qualified as DLT: 1) CTCAE Grade ≥2 decrease in cardiac left ventricular function 2) CTCAE Grade 2 diarrhoea lasting for ≥7 days, despite appropriate use of standard antidiarrheal therapy based on Protocol Amendment 1 dated 22 Oct 2013 3) CTCAE Grade ≥3 diarrhoea despite appropriate use of standard anti-diarrheal therapy for at least 2 days. 4) CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days 5) CTCAE Grade ≥3 rash despite standard medical management. 6) CTCAE Grade ≥3 fatigue lasting more than 7 days. 7) All other AEs of CTCAE Grade ≥3 (except alopecia and allergic reaction) that led to an interruption of afatinib and/or cetuximab dosing for more than 14 days until recovery to baseline or Grade 1, whichever was higher. 8) CTCAE Grade 4 hypomagnesemia or Grade 3 hypomagnesemia with clinically-significant sequelae | First 21-day treatment cycle |
| MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Cetuximab). | Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with DLTs during the first treatment cycle (Dose escalation part). | First treatment cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities During All Treatment Cycles | Number of patients with DLT occuring during all treatment cycle is presented | All treatment cycle (each treatment cycle of 21 days) |
| Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Cetuximab) |
Not provided
Inclusion criteria:
Part A only
Patients must have advanced malignant solid tumours that are metastatic or unresectable
At least one measurable or evaluable (non-measurable) lesion per RECIST 1.1 Part B only
Patients must have:
measurable disease per RECIST 1.1
diagnosis of one of the following
or
Age 18 years or older
Written informed consent that is consistent with ICH-GCP guidelines and local law.
Histological/Cytological confirmed diagnosis of malignant solid tumours (exclusion of sarcomas)
Advanced disease for whom standard treatment is ineffective or no longer effective
Recovered from previous therapy related AE to </= Grade 1 at the study entry (except, for stable sensory neuropathy </= Grade 2 and alopecia)
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Adequate organ function as defined by the following criteria:
Exclusion criteria:
Chemotherapy, biological therapy or investigational agents within 4 weeks prior to the start of study treatment.
Hormonal anti-cancer treatment within 2 weeks prior to the start of study treatment (continued use of anti-androgens and/or gonadorelin analogues [LHRH] is permitted)
Radiotherapy within 4 weeks prior to the start of study treatment, except as follows:
Major surgery (as judged by the investigator) within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
Known hypersensitivity to afatinib or the excipients of any of the trial drugs
History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior start treatment.
Female patients of childbearing potential who:
Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
Requiring treatment with any of the prohibited concomitant medications listed in the protocol that can not be stopped for the duration of trial participation
Known pre-existing interstitial lung disease
Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption)
Active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment.
Meningeal carcinomatosis
Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids or have been on stable dose of corticosteroids for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment.
Any SPC listed contra-indications for cetuximab
Use of alcohol or drugs incompatible with patient participation in the study in the investigator's opinion.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.122.33001 Boehringer Ingelheim Investigational Site | Villejuif | France | ||||
| 1200.122.34001 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30278378 | Derived | Gazzah A, Boni V, Soria JC, Calles A, Even C, Doger B, Mahjoubi L, Bahleda R, Ould-Kaci M, Esler A, Nazabadioko S, Calvo E. A phase 1b study of afatinib in combination with standard-dose cetuximab in patients with advanced solid tumours. Eur J Cancer. 2018 Nov;104:1-8. doi: 10.1016/j.ejca.2018.07.011. Epub 2018 Oct 1. |
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Uncontrolled, open label, 3+3 dose escalation (Part A) study of afatinib in combination with cetuximab, followed by an expansion phase in 3 cohorts of patients (Part B). Adverse Event (AE).
CTCAE: Common Terminology Criteria for Adverse Events
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Afatinib 30mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patients were administered 30 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
| FG001 | Afatinib 40mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patient were administered 40 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400 mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set: This patient set includes all patients enrolled in the trial who were documented to have taken at least one dose of study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Afatinib 30mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patients were administered 30 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib). | Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD is defined as the highest dose level at which less than 33% of the patients experience DLT in first treatment cycle. | Dose finding cohort treated set: This patient set includes all patients enrolled in part A of the trial who were documented to have taken at least one dose of study medication. | Posted | Number | mg | First 21 days treatment cycle |
|
From first drug administration until 28 days after last drug administration, up to 19 months.
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 | Afatinib 30mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patients were administered 30 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000077716 | Afatinib |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
once per day |
|
MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles. |
| All treatment cycle (each treatment cycle of 21 days) |
| Best Overall Response | Best overall response (according to RECIST version 1.1) was defined as the best response recorded at any time from the first administration of afatinib or cetuximab to the End of Treatment (EOT). As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
| Objective Response | Objective response was defined as the proportion of patients with measurable disease having at least a best overall response of complete response (CR) or partial response (PR), according to RECIST version 1.1. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
| Disease Control Rate | For patients with measurable disease, disease control was defined as the proportion of patients having at least a best overall response of CR, PR or stable disease (SD). As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
| Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Afatinib) | MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles. | All treatment cycle (each treatment cycle of 21 days) |
| Madrid |
| Spain |
| Withdrawal by Subject |
|
| Other than stated above |
|
| Afatinib 40mg+Cetuximab 250 mg/m² |
In each 21 day treatment cycle, patient were administered 40 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400 mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Afatinib 40mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patient were administered 40 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400 mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. |
|
|
| Primary | Dose Limiting Toxicities During Cycle 1 | Number of Patients With Dose Limiting Toxicity (DLT) Occurring during Cycle 1. The following drug related AEs qualified as DLT: 1) CTCAE Grade ≥2 decrease in cardiac left ventricular function 2) CTCAE Grade 2 diarrhoea lasting for ≥7 days, despite appropriate use of standard antidiarrheal therapy based on Protocol Amendment 1 dated 22 Oct 2013 3) CTCAE Grade ≥3 diarrhoea despite appropriate use of standard anti-diarrheal therapy for at least 2 days. 4) CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days 5) CTCAE Grade ≥3 rash despite standard medical management. 6) CTCAE Grade ≥3 fatigue lasting more than 7 days. 7) All other AEs of CTCAE Grade ≥3 (except alopecia and allergic reaction) that led to an interruption of afatinib and/or cetuximab dosing for more than 14 days until recovery to baseline or Grade 1, whichever was higher. 8) CTCAE Grade 4 hypomagnesemia or Grade 3 hypomagnesemia with clinically-significant sequelae | Dose finding cohort treated set. | Posted | Number | Participants | First 21-day treatment cycle |
|
|
|
| Primary | MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Cetuximab). | Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with DLTs during the first treatment cycle (Dose escalation part). | Dose finding cohort treated set | Posted | Number | mg/m2 | First treatment cycle |
|
|
|
| Secondary | Dose Limiting Toxicities During All Treatment Cycles | Number of patients with DLT occuring during all treatment cycle is presented | Treated Set | Posted | Number | Participants | All treatment cycle (each treatment cycle of 21 days) |
|
|
|
| Secondary | Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Cetuximab) | MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles. | Treated Set | Posted | Number | mg/m2 | All treatment cycle (each treatment cycle of 21 days) |
|
|
|
| Secondary | Best Overall Response | Best overall response (according to RECIST version 1.1) was defined as the best response recorded at any time from the first administration of afatinib or cetuximab to the End of Treatment (EOT). As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. | Treated set | Posted | Number | Percentage of participants | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
|
|
|
| Secondary | Objective Response | Objective response was defined as the proportion of patients with measurable disease having at least a best overall response of complete response (CR) or partial response (PR), according to RECIST version 1.1. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. | Treated set | Posted | Number | Percentage of participants | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
|
|
|
| Secondary | Disease Control Rate | For patients with measurable disease, disease control was defined as the proportion of patients having at least a best overall response of CR, PR or stable disease (SD). As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression | Treated set | Posted | Number | Percentage of participants | Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months |
|
|
|
| Secondary | Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Afatinib) | MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles. | Treated Set | Posted | Number | mg | All treatment cycle (each treatment cycle of 21 days) |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Afatinib 40mg+Cetuximab 250 mg/m² | In each 21 day treatment cycle, patient were administered 40 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400 mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose. | 31 | 55 | 54 | 55 |
| EG002 | All Patients | Patients who were administered Afatinib 30mg+cetuximab 250 mg/m² plus the patients who were administered Afatinib 40mg+cetuximab 250 mg/m². | 32 | 58 | 57 | 58 |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
|
| Deafness unilateral | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Nervous system disorder | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Female genital tract fistula | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Bronchostenosis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Ophthalmoplegia | Eye disorders | MedDRA 19.0 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 19.0 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 19.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Xerosis | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Nail ridging | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Xeroderma | Skin and subcutaneous tissue disorders | MedDRA 19.0 | 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.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
|
| Stable Disease (SD) |
|
| Progressive disease (PD) |
|
| Not evaluable (NE)/Missing |
|