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Afatinib in NSCLC With HER2 Mutation (NICHE)

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ClinicalTrials.gov Identifier: NCT02369484
Recruitment Status : Completed
First Posted : February 24, 2015
Results First Posted : March 1, 2019
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition NSCLC
Intervention Drug: Afatinib
Enrollment 13
Recruitment Details ETOP/7-14 NICHE trial was activated in December 2014. The first patient was enrolled on September 2015 while the last one on August 2016, before accrual was suspended in October 2016. Patients were enrolled in 3 centers (Netherlands Cancer Institute of Amsterdam, Vall d' Herbon Univesity Hospital (Spain) and Universitatsklinikum Koln (Germany)).
Pre-assignment Details All 13 patients eligible for enrollment received treatment
Arm/Group Title Afatinib
Hide Arm/Group Description Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Period Title: Overall Study
Started 13
Completed 13
Not Completed 0
Arm/Group Title Afatinib
Hide Arm/Group Description

Afatinib 40 mg p.o./day until tumour progression or lack of tolerability

Afatinib: 40mg p.o./ day until documented progression or unacceptable toxicity

Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants
59
(39 to 82)
[1]
Measure Description: Age of patient at enrollment
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
9
  69.2%
Male
4
  30.8%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Netherlands Number Analyzed 13 participants
7
Germany Number Analyzed 13 participants
3
Spain Number Analyzed 13 participants
3
Smoking history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Current
1
   7.7%
Former
4
  30.8%
Never
8
  61.5%
ECOG Performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
0
7
  53.8%
1
4
  30.8%
2
2
  15.4%
[1]
Measure Description:

PS 0: Fully active, able to carry on all pre-disease performance without restriction.

PS 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.

PS 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

PS 3: Capable of only limited self care, confined to bed or chair more than 50% of waking hours.

PS 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.

T parameter   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
T1b
1
   7.7%
T2a
3
  23.1%
T3
3
  23.1%
T4
6
  46.2%
[1]
Measure Description:

Primary tumor (T)

TX: Main tumor cannot be measured. T0: Main tumor cannot be found. T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.

N parameter   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
N0
5
  38.5%
N2
3
  23.1%
N3
5
  38.5%
[1]
Measure Description:

Regional lymph nodes (N)

NX: Cancer in nearby lymph nodes cannot be measured. N0: There is no cancer in nearby lymph nodes. N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.

M parameter   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
M0
1
   7.7%
M1a
6
  46.2%
M1b
6
  46.2%
[1]
Measure Description:

Distant metastasis (M)

MX: Metastasis cannot be measured. M0: Cancer has not spread to other parts of the body. M1: Cancer has spread to other parts of the body.

TNM staging   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
T1b-N3-M1b
1
   7.7%
T2a-N0-M1a
1
   7.7%
T2a-N2-M1b
1
   7.7%
T2a-N3-M1b
1
   7.7%
T3-N0-M1b
1
   7.7%
T3-N2-M1a
1
   7.7%
T3-N3-M1b
1
   7.7%
T4-N0-M1a
3
  23.1%
T4-N2-M0
1
   7.7%
T4-N3-M1a
1
   7.7%
T4-N3-M1b
1
   7.7%
[1]
Measure Description:

The TNM system is the most widely used cancer staging system.

In the TNM system:

The T refers to the size and extent of the main tumor. The main tumor is usually called the primary tumor.

The N refers to the the number of nearby lymph nodes that have cancer. The M refers to whether the cancer has metastasized. This means that the cancer has spread from the primary tumor to other parts of the body.

When your cancer is described by the TNM system, there will be numbers after each letter that give more details about the cancer—for example, T1N0MX or T3N1M0.

Type of prior platinum treatment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Adjuvant
2
  15.4%
Advanced disease
11
  84.6%
1.Primary Outcome
Title Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)
Hide Description

Disease control (DC) is defined as complete or partial response, or disease stabilisation lasting at least 12 weeks.

Disease control will be determined using RECIST 1.1 criteria:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.

Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

Time Frame at interim (after the first 9 pts have been followed for 12 weeks) & final analysis (approx. 40 months after inclusion of first pt)
Hide Outcome Measure Data
Hide Analysis Population Description
The statistical design of the trial, included an interim efficacy analysis to be performed as soon as the 12-week status of the first 9 patients was available. So, the interim analysis was performed but up to then 13 patients have been enrolled.
Arm/Group Title Afatinib
Hide Arm/Group Description:
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
Analysis of all enrolled patients (N=13) Number Analyzed 13 participants
DC at 12 weeks- "Yes"
7
  53.8%
DC at 12 weeks- "No"
6
  46.2%
Interim analysis patients (N=9) Number Analyzed 9 participants
DC at 12 weeks- "Yes"
4
  44.4%
DC at 12 weeks- "No"
5
  55.6%
2.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) is defined as the time from date of enrollment until documented progression or death, if progression is not documented. Censoring will occur at the last tumor assessment only if patients is lost to follow-up
Time Frame Time assessed from the date of enrolment until documented progression or death (max 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled up to trial termination
Arm/Group Title Afatinib
Hide Arm/Group Description:
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: weeks
15.9
(6.0 to 35.4)
3.Secondary Outcome
Title Objective Response
Hide Description

Objective response is defined as best overall response (CR or PR) across all assessment time-points during the period from enrollment to termination of trial treatment. Objective response to afatinib treatment will be determined using RECIST 1.1 criteria:

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.

Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

Time Frame Assessed across all time-points during the period from enrolment to termination of trial treatment (max. 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled in the trial up to trial termination. From the total of 13 patients, one patient had only one tumor assessment and was classified as "Non-Evaluable", since she cannot be accounted for the Objective Response rate.
Arm/Group Title Afatinib
Hide Arm/Group Description:
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
Objective response (CR or PR)
1
   7.7%
Stable disease
6
  46.2%
Progression disease
5
  38.5%
Non-evaluable
1
   7.7%
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) is defined as the time from the date of enrollment until death from any cause. Censoring will occur at the last follow-up.
Time Frame Time assessed from the date of enrolment until death (max 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled in the trial up to trial termination
Arm/Group Title Afatinib
Hide Arm/Group Description:
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: weeks
56.0
(16.3 to 100)
5.Secondary Outcome
Title Toxicities of Treatment
Hide Description Adverse events classified according to NCI CTCAE version 4.
Time Frame Assessed from the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled in the trial up to trial termination
Arm/Group Title Afatinib
Hide Arm/Group Description:
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
Experienced AE/SAE
13
 100.0%
No AE/SAE
0
   0.0%
Time Frame From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib
Hide Arm/Group Description

Afatinib 40 mg p.o./day until tumour progression or lack of tolerability

Afatinib: 40mg p.o./ day until documented progression or unacceptable toxicity

All-Cause Mortality
Afatinib
Affected / at Risk (%)
Total   1/13 (7.69%) 
Show Serious Adverse Events Hide Serious Adverse Events
Afatinib
Affected / at Risk (%)
Total   5/13 (38.46%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/13 (7.69%) 
Cardiac disorders   
Pericardial effusion  1  1/13 (7.69%) 
Gastrointestinal disorders   
Diarrhea  1  1/13 (7.69%) 
Metabolism and nutrition disorders   
Dehydration  1  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders   
Muscle weakness lower limb  1  1/13 (7.69%) 
Renal and urinary disorders   
Acute kidney injury  1  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/13 (7.69%) 
Epistaxis  1  1/13 (7.69%) 
Pleural effusion  1  1/13 (7.69%) 
1
Term from vocabulary, NCI CTCAE Version 4.
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Afatinib
Affected / at Risk (%)
Total   13/13 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  2/13 (15.38%) 
Cardiac disorders   
Ventricular arrhythmia  1  1/13 (7.69%) 
Eye disorders   
Dry eye  1  2/13 (15.38%) 
Gastrointestinal disorders   
Diarrhea  1  11/13 (84.62%) 
Mucositis oral  1  4/13 (30.77%) 
Abdominal pain  1  3/13 (23.08%) 
Vomiting  1  3/13 (23.08%) 
Constipation  1  1/13 (7.69%) 
Dry mouth  1  1/13 (7.69%) 
Nausea  1  1/13 (7.69%) 
General disorders   
Fatigue  1  3/13 (23.08%) 
Flu like symptoms  1  2/13 (15.38%) 
Non-cardiac chest  1  2/13 (15.38%) 
Malaise  1  1/13 (7.69%) 
Infections and infestations   
Paronyclia  1  5/13 (38.46%) 
Bladder infection  1  1/13 (7.69%) 
Eye infection  1  1/13 (7.69%) 
Sinusitis  1  1/13 (7.69%) 
Tooth infection  1  1/13 (7.69%) 
Urinary track infection  1  1/13 (7.69%) 
Nail infection  1  1/13 (7.69%) 
Papulopustular rash  1  1/13 (7.69%) 
Other (tonsillitis)  1  1/13 (7.69%) 
Investigations   
GGT increased  1  2/13 (15.38%) 
Asparate aminotransferase increased  1  1/13 (7.69%) 
Creatine increased  1  1/13 (7.69%) 
Platelet count decreased  1  1/13 (7.69%) 
Weight loss  1  1/13 (7.69%) 
Metabolism and nutrition disorders   
Hyperkalemia  1  1/13 (7.69%) 
Hypermagnesemia  1  1/13 (7.69%) 
Hypoalbuminemia  1  1/13 (7.69%) 
Hypomagnesemia  1  1/13 (7.69%) 
Hyponatremia  1  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders   
Arthalgia  1  1/13 (7.69%) 
Back pain  1  1/13 (7.69%) 
Bone pain  1  1/13 (7.69%) 
Myalgia  1  1/13 (7.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor pain  1  1/13 (7.69%) 
Nervous system disorders   
Headache  1  2/13 (15.38%) 
Dysgeusia  1  1/13 (7.69%) 
Peripheral sensory neuropathy  1  1/13 (7.69%) 
Other (paraplegia from Th4))  1  1/13 (7.69%) 
Renal and urinary disorders   
Cystitis noninfective  1  1/13 (7.69%) 
Urinary incontinence  1  1/13 (7.69%) 
Urinary track obstruction  1  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  3/13 (23.08%) 
Cough  1  2/13 (15.38%) 
Epistaxis  1  1/13 (7.69%) 
Pleural effusion  1  1/13 (7.69%) 
Alopecia  1  1/13 (7.69%) 
Skin and subcutaneous tissue disorders   
Erythema multiforme  1  4/13 (30.77%) 
Rash acneiform  1  4/13 (30.77%) 
Dry skin  1  3/13 (23.08%) 
Other  1  2/13 (15.38%) 
Vascular disorders   
Hypertension  1  1/13 (7.69%) 
1
Term from vocabulary, NCI CTCAE Version 4.
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Heidi Roschitzki-Voser, Lead Trial Activities
Organization: European Thoracic Oncology Platform (ETOP)
Phone: +41 31 511 94 18
Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT02369484     History of Changes
Other Study ID Numbers: ETOP 7-14
2014-005098-35 ( EudraCT Number )
1200.230 ( Other Identifier: Boehringer Ingelheim )
SNCTP000001674 ( Registry Identifier: Swiss National Clinical Trials Portal (SNCTP) )
First Submitted: February 17, 2015
First Posted: February 24, 2015
Results First Submitted: February 6, 2018
Results First Posted: March 1, 2019
Last Update Posted: June 13, 2019