Afatinib as second-line therapy for lung cancer with EGFR mutatio

Phase 1

Conditions: Metastatic non-small cell lung cancer harbouring an EGFR mutation (Del 19 or L858R)
MedDRA version: 17.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001077-14-RO

Lead Sponsor: Boehringer Ingelheim RCV GmbH & Co KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 70

Inclusion Criteria

1. Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
2. Documented EGFR mutation (L858R and/or Deletion 19) with no other known EGFR mutation.
3. Measureable disease according to RECIST 1.1.
4. Radiologically confirmed progression or recurrence of disease during or following first line therapy with a platinum-based chemotherapy regimen.
5. Age >18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
7. Adequate organ function, defined as all of the following: Absolute neutrophil count (ANC) > 1500 / mm3, Platelet count >75,000 / mm3, Estimated creatinine clearance > 45ml / min, Total Bilirubin < 1.5 times upper limit of institution normal, Aspartate amino transferase (AST) and alanine amino transferase (ALT) < three times the upper limit of institution normal (ULN) (if related to liver metastases < five times ULN).
8. Recovered from any previous therapy-related toxicity to less than or equal to CTCAE Grade 1 at study entry (except for alopecia and stable sensory neuropathy which must be less than or equal to CTCAE Grade 2).
9. Life expectancy of at least three months.
10. Written informed consent that is consistent with ICH-GCP guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112

Exclusion Criteria

1. More than one line of prior therapy for disease.
2. Previously received less than 3 cycles of platinum-based chemotherapy due to toxicity and/or intolerance of treatment.
3. Previous treatment with any EGFR targeting TKI or antibody.
4. Chemotherapy, biological therapy or investigational agents within three weeks prior to the start of study treatment.
5. Hormonal treatment within two weeks prior to start of study treatment.
6. Radiotherapy within 4 weeks prior to study treatment, except for palliative radiation to target organs other than chest and single dose palliative treatment for symptomatic metastasis.
7. Major surgery within 4 weeks before starting study treatment or surgery scheduled during the projected course of the study.
8. Known hypersensitivity to afatinib or the excipients of afatinib.
9. 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 or myocardial infarction within 6 months prior to study treatment.
10. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 28 days after treatment has ended.
11. Female patients of childbearing potential who are nursing or pregnant or do not agree to submit to pregnancy testing required by this protocol.
12. 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.
13. Previous or concomitant malignancies at other sites, except; a) effectively treated non-melanoma skin cancers, b) effectively treated carcinoma in situ of the cervix, c) effectively treated ductal carcinoma in situ, d) other effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
14. Requiring treatment with any of the listed prohibited concomitant medications
that cannot be stopped for the duration of trial participation.
15. Known pre-existing interstitial lung disease.
16. 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).
17. 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.
18. Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment.
19. Meningeal carcinomatosis.
20. Presence or history of brain or subdural metastases, unless patient has completed local therapy and has discontinued the use of corticosteroids or has 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Objective tumour response (Complete Response (CR), Partial Response (PR)) according to RECIST 1.1;Secondary Objective: Progression free survival (PFS), Disease control (CR, PR, Stable Disease (SD));Primary end point(s): 1: Objective tumour response (Complete response (CR), Partial Response (PR)) according to RECIST 1.1<br>;Timepoint(s) of evaluation of this end point: 1: 24 weeks<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1: Progression free survival (PFS) according to RECIST 1.1<br><br>2: Disease control (CR, PR, Stable Disease (SD)) according to RECIST 1.1<br>;Timepoint(s) of evaluation of this end point: 1: 33 months<br><br>2: 33 months<br>

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