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

NCT00711594 | Completed Phase 2 Results

• 1 other identifier: 1200.33
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 20

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

Outcome Measures

Primary Outcomes (2)

• Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE

  start of treatment to end of treatment

• Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)

  The objective response (complete response \[CR\] and partial response \[PR\]) was defined as determined by the RECIST according to the best response to study treatment.

  Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation), up to 41.3 months

Secondary Outcomes (15)

• Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration

  AUC0-24: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00 on Day 1-2 in Course 1; AUCtau,ss: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00, 48:00, 72:00 on Day 28-31 in Course 1

• Phase II Step: Clinical Benefit

  Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months

• Phase II Step: Time to Objective Response

  Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months

• Phase II Step: Duration of Objective Response

  Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months

• Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings

  Screening visit

Study Arms (2)

BIBW 2992 MA2

EXPERIMENTAL

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.

Drug: BIBW 2992 MA2 40mg/day; Drug: BIBW 2992 MA2 50mg/day; Drug: BIBW 2992 MA2 20mg/day

BIBW 2992 QD

EXPERIMENTAL

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.

Drug: BIBW 2992 QD

Interventions

BIBW 2992 MA2 40mg/day DRUG

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

BIBW 2992 MA2

BIBW 2992 MA2 50mg/day DRUG

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

BIBW 2992 MA2

BIBW 2992 MA2 20mg/day DRUG

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

BIBW 2992 MA2

BIBW 2992 QD DRUG

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

BIBW 2992 QD

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase II step;
• 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.
• 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
• Male or female patients age \>=20 years at the enrolment.
• Life expectancy of at least three (3) months after the start of administration of the investigational drug.
• Eastern Cooperative Oncology Group (ECOG) performance Score 0 or 1.
• 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.
• Written informed consent that is consistent with ICH-GCP guidelines.

You may not qualify if:

• Phase II step;
• Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within two weeks before starting the study medication.
• 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.
• 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.
• Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of.
• Brain tumor, and / or brain metastases, which are symptomatic or requiring treatment at the enrolment.
• 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).
• 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.
• Coelomic fluid retention (such as pleural effusion, ascites or pericardial effusion) requiring treatment.
• Uncontrolled concomitant diseases (e.g. diabetes mellitus, hypertension etc).
• History of serious drug hypersensitivity.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (20)

1200.33.010 Boehringer Ingelheim Investigational Site

Akashi, Hyogo, Japan

Location

1200.33.001 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, Japan

Location

1200.33.007 Boehringer Ingelheim Investigational Site

Fukuoka, Fukuoka, Japan

Location

1200.33.013 Boehringer Ingelheim Investigational Site

Hidaka, Saitama, Japan

Location

1200.33.011 Boehringer Ingelheim Investigational Site

Kanazawa, Ishikawa, Japan

Location

1200.33.003 Boehringer Ingelheim Investigational Site

Kashiwa, Chiba, Japan

Location

1200.33.019 Boehringer Ingelheim Investigational Site

Kobe, Hyogo, Japan

Location

1200.33.008 Boehringer Ingelheim Investigational Site

Koto-ku, Tokyo, Japan

Location

1200.33.020 Boehringer Ingelheim Investigational Site

Matsuyama, Ehime, Japan

Location

1200.33.006 Boehringer Ingelheim Investigational Site

Miyakojima-ku, Osaka, Japan

Location

1200.33.004 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

Location

1200.33.017 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

Location

1200.33.016 Boehringer Ingelheim Investigational Site

Niigata, Niigata, Japan

Location

1200.33.009 Boehringer Ingelheim Investigational Site

Okayama, Okayama, Japan

Location

1200.33.005 Boehringer Ingelheim Investigational Site

Osaka-Sayama, Osaka, Japan

Location

1200.33.018 Boehringer Ingelheim Investigational Site

Sakai, Osaka, Japan

Location

1200.33.015 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, Japan

Location

1200.33.012 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, Japan

Location

1200.33.002 Boehringer Ingelheim Investigational Site

Sunto-gun, Shizuoka, Japan

Location

1200.33.014 Boehringer Ingelheim Investigational Site

Yufu, Oita, Japan

Location

Related Publications (2)

• 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.

  PMID: 23816963 DERIVED

• 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.

  PMID: 22071596 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 9, 2008
• Study Start: April 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: January 15, 2015
• Results First Posted: November 13, 2013

Record last verified: 2015-01

Locations

JP (20)