LUX-Lung 4: BIBW 2992 (Afatinib) Phase I Trial in Advanced Non Small Cell Lung Cancer Patients & Phase II Trial in Non Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

NCT ID: NCT00711594

Last Updated: 2015-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2013-11-30

Brief Summary

The objective of the Phase I step is to estimate the MTD at a dose level up to 50 mg/day (i.e., overseas recommended Phase II dose) in patients with advanced NSCLC and to determine the recommended dose for the Phase II step.

The objective of the Phase II step is to estimate the efficacy of BIBW 2992 monotherapy in patients with first generation EGFR-TKI-resistant advanced NSCLC at the recommended dose determined in the Phase I step.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BIBW 2992 MA2

Phase I step: Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally. Escalating doses of BIBW 2992 starting at 20mg daily.

Group Type: EXPERIMENTAL

BIBW 2992 MA2 40mg/day

Intervention Type: DRUG

Phase I step: Increased dose cohorts from low dose to MTD

BIBW 2992 MA2 50mg/day

Intervention Type: DRUG

Phase I step: Increased dose cohorts from low dose to MTD

BIBW 2992 MA2 20mg/day

Intervention Type: DRUG

Phase I step: Increased dose cohorts from low dose to MTD

BIBW 2992 QD

Phase II step: Patients start continuous once daily oral treatment of BIBW 2992 at high dose, until progression or undue Adverse Events (AEs) develop. Patients can be dose-reduced up to two times if needed after temporary discontinuation of treatment due to drug-related AEs.

Group Type: EXPERIMENTAL

BIBW 2992 QD

Intervention Type: DRUG

Phase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs.

Interventions

BIBW 2992 MA2 40mg/day

Phase I step: Increased dose cohorts from low dose to MTD

Intervention Type: DRUG

BIBW 2992 MA2 50mg/day

Phase I step: Increased dose cohorts from low dose to MTD

Intervention Type: DRUG

BIBW 2992 MA2 20mg/day

Phase I step: Increased dose cohorts from low dose to MTD

Intervention Type: DRUG

BIBW 2992 QD

Phase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Phase II step;

1. Patients with pathologic confirmation of NSCLC with tissue diagnosis or cytologic diagnosis, whose NSCLCs are locally advanced or metastatic Stage III-B / IV adenocarcinoma, and are inoperable and incurable with radiotherapy.

2. Patients who have received the following pretreatments for the treatment of relapsed or metastatic NSCLC.

• Patients who have received at least one but not more than two lines of chemotherapy. ("Chemotherapy" means only the first line (doublet chemotherapies including a platinum) and/or the second line (single chemotherapy except for a platinum) of cytotoxic chemotherapy according to the standard chemotherapies, and erlotinib (Tarceva®) and gefitinib (Iressa®) should be excluded. One of the chemotherapy regimens must have been platinum-based. In addition, only one prior cytotoxic chemotherapy treatment regimen is allowed after adjuvant chemotherapy containing a platinum. More than two prior cytotoxic chemotherapy treatment regimens are not allowed.)
• After the above chemotherapies, patients who once got clinical benefits (i.e. complete response, partial response or stable disease) but progressed following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®) as the most recent treatment. ("Clinical benefit" and "progression" should be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI). In addition, "at least 12 weeks of treatment" should be 9 weeks or more as the actual "treatment period except for treatment pause due to adverse events and other reasons.) As long as the treatment is erlotinib or gefitinib monotherapy, patients can receive multiple regimens of either or both treatments, but one of the regimens should be for at least 12 weeks

3. Male or female patients age >=20 years at the enrolment.

4. Life expectancy of at least three (3) months after the start of administration of the investigational drug.

5. Eastern Cooperative Oncology Group (ECOG) performance Score 0 or 1.

6. Patients with at least one tumor lesion that can accurately be measured by CT or MRI in at least one dimension with longest diameter to be recorded as no less than double the slice thickness and >=10 mm.

7. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion Criteria

Phase II step;

1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within two weeks before starting the study medication.

2. Patients who have received definitive thoracic radiotherapy with curative intent. Patients who have received radiotherapy or other investigational drugs (non-oncological) within four weeks before enrolment.

3. Significant gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >2 diarrhea of any etiology at the enrolment.

4. Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of.

5. Brain tumor, and / or brain metastases, which are symptomatic or requiring treatment at the enrolment.

6. Other malignancies diagnosed within the past five years (other than carcinoma in situ of gastric cancer, colon cancer and cervical cancer, and non melanomatous skin cancer).

7. History of uncontrolled cardiac disease such as angina or myocardial infarction within the past 6 months at the enrolment, congestive heart failure including New York Heart Association (NYHA) functional classification of 3, or arrhythmia requiring treatment.

8. Coelomic fluid retention (such as pleural effusion, ascites or pericardial effusion) requiring treatment.

9. Uncontrolled concomitant diseases (e.g. diabetes mellitus, hypertension etc).

10. History of serious drug hypersensitivity.

11. Patients who do not have sufficient baseline organ function and whose laboratory data do not meet the following criteria at the enrolment.11

• Haemoglobin count >=9.0 g/dL
• Absolute neutrophil count (ANC) >=1500 / mm3
• Platelet count >=100 000 / mm3
• Serum creatinine <=1.5 mg/dL
• Total bilirubin <=1.5 mg/dL
• Aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) <=2.5x upper limit of normal range (if related to liver metastases <=2.5x upper limit of normal also)
• PaO2 >=60torr or SpO2 >=92%
• LVEF as measured by echocardiography or multigated blood pool imaging of the heart (MUGA scan) >=50%
• QTc interval <0.47 second

12. Patients who disagree with using a medically acceptable method of contraception during the administration of the investigational drug and for at least 6 months after the end of administration.

13. Pregnant or breast-feeding women, or women suspected of being pregnant.

14. Known positive HBs antigen, HCV antibody, or HIV antibody test.

15. Known or suspected active drug or alcohol abuse.

16. Other patients judged ineligible for enrolment in the study by the investigator (sub-investigator).

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1200.33.010 Boehringer Ingelheim Investigational Site

Akashi, Hyogo, , Japan

1200.33.001 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, , Japan

1200.33.007 Boehringer Ingelheim Investigational Site

Fukuoka, Fukuoka, , Japan

1200.33.013 Boehringer Ingelheim Investigational Site

Hidaka, Saitama, , Japan

1200.33.011 Boehringer Ingelheim Investigational Site

Kanazawa, Ishikawa, , Japan

1200.33.003 Boehringer Ingelheim Investigational Site

Kashiwa, Chiba, , Japan

1200.33.019 Boehringer Ingelheim Investigational Site

Kobe, Hyogo, , Japan

1200.33.008 Boehringer Ingelheim Investigational Site

Koto-ku, Tokyo, , Japan

1200.33.020 Boehringer Ingelheim Investigational Site

Matsuyama, Ehime, , Japan

1200.33.006 Boehringer Ingelheim Investigational Site

Miyakojima-ku, Osaka, , Japan

1200.33.004 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

1200.33.017 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

1200.33.016 Boehringer Ingelheim Investigational Site

Niigata, Niigata, , Japan

1200.33.009 Boehringer Ingelheim Investigational Site

Okayama, Okayama, , Japan

1200.33.005 Boehringer Ingelheim Investigational Site

Osaka-Sayama, Osaka, , Japan

1200.33.018 Boehringer Ingelheim Investigational Site

Sakai, Osaka, , Japan

1200.33.015 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, , Japan

1200.33.012 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

1200.33.002 Boehringer Ingelheim Investigational Site

Sunto-gun, Shizuoka, , Japan

1200.33.014 Boehringer Ingelheim Investigational Site

Yufu, Oita, , Japan

Countries

Japan

References

Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1.

Reference Type: DERIVED

PMID: 23816963 (View on PubMed)

Murakami H, Tamura T, Takahashi T, Nokihara H, Naito T, Nakamura Y, Nishio K, Seki Y, Sarashina A, Shahidi M, Yamamoto N. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol. 2012 Apr;69(4):891-9. doi: 10.1007/s00280-011-1738-1. Epub 2011 Nov 10.

Reference Type: DERIVED

PMID: 22071596 (View on PubMed)

Other Identifiers

1200.33

Identifier Type: -

Identifier Source: org_study_id