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Non-Small Cell Lung CancerPhase 2NSCLCNCT01542437

Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non-small Cell Lung Cancer

A Phase 2 study testing BIBW 2992 in people with Non-Small Cell Lung Cancer and EGFR, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with stage IIIB and IV lung adenocarcinoma and progression to first-line chemotherapy were enrolled to receive afatinib 40 mg/day. Mutational EGFR and HER-2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Non-Small Cell Lung Cancer, EGFR, HER-2
What is being tested?
BIBW 2992
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteMexico
Study dates
Jan 2012to Jun 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of lung cancer non-small cell (stage IIIB or IV) inoperable, locally advanced, recurrent or metastatic, histologically or cytologically documented.
  • The patient must present evidence of measurable disease.
  • 18 years of age or older.
  • ECOG performance status of 0-2
  • Life expectancy at least 12 weeks.
  • lung cancer patients with advanced non-small cell, stage IIIB / IV who have received at least one cycle of systemic chemotherapy standard platinum-based first-or second-line fault has been documented that treatment.
Show all 15Show fewer
  • are admissible 3 or more prior chemotherapy regimens. Patients must have recovered from any toxic effects and should have passed at least 2 weeks after the last dose prior to registration (14 days for vinorelbine and other vinca alkaloids or gemcitabine). Patients in the opinion of the investigator are fully recovered from surgery for 4 weeks at least, can also be considered for the study. Patients must have recovered from any severe toxicity (CTC ≤ 1) caused by any previous therapy.
  • granulocyte count ≥ 1.5x 109 / L and platelet count> 100 × 109 / L.
  • serum bilirubin should be ≤ 1.5 X ULN
  • AST and / or ALT ≤ 2 ULN (or ≤ 5 x ULN when clearly attributable to the presence of liver metastases).
  • Serum creatinine ≤ 1.5 (ULN) or creatinine clearance ≥ 60ml/min
  • Ability to comply with study procedures and monitoring.
  • Of all women of childbearing potential should be obtained a negative pregnancy test within 72 hours before the start of therapy.
  • Patients with reproductive potential must use effective contraception.
  • Written informed consent (signed) to participate in the study.

Who cannot join

  • Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, liver disease, renal or metabolic).
  • Pre-treatment with systemic anti-tumor therapy with EGFR inhibitors (tyrosine kinase inhibitors).
  • Any other malignancy within the previous 5 years (except for carcinoma in situ of the cervix or skin cancer adequately treated basal cell type).
  • Excluded patients with brain metastases or spinal cord compression of newly diagnosed and / or have not been definitively treated with surgery and / or radiation, supporting both patients with CNS metastases or spinal cord compression previously diagnosed and treated with evidence of stable disease (clinically stable on imaging studies) for a minimum of 2 months.
  • Any significant ophthalmologic abnormality, especially severe syndrome of dry eye, keratoconjunctivitis sicca, Sjogren's syndrome, severe keratitis exposure and any other condition that may increase the risk of corneal epithelial damage. We do not recommend the use of contact lenses during the study. The decision to continue with the use of contact lenses should be discussed with the treating oncologist and the patient's ophthalmologist.
  • Patients unable to take oral medication, requiring intravenous nutrition, which have undergone prior surgical procedures affecting absorption, or who have active peptic ulceration.
  • lactating women.

Trial locations and contacts

1 site in 1 country.

Mexico1 site

  • National Cancer Institute of Mexico

    Mexico City, Mexico City, 14080

Other trials in Mexico

About this study

Official title: Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non Small Cell Lung Cancer in Advanced Stage, Which Have Progressed to Chemotherapy. Analysis of Mutations in EGFR and Number of Copies of HER-2

Patients with stage IIIB and IV lung adenocarcinoma and progression to first-line chemotherapy were enrolled to receive afatinib 40 mg/day. Mutational EGFR and HER-2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Plasma HGF levels were measured by ELISA before and 2 months (mo) after the start of treatment. We assessed changes in serum HGF levels and their association with objective response rate (ORR), PFS and overall survival (OS).

Read the detailed description

Lung cancer is the main cause of cancer-related mortality worldwide, accounting for 1.6 million deaths in 2012. Non-small-cell lung cancer (NSCLC) histology comprises ap-proximately 85% of cases. At the time of diagnosis, 75% of the patients have locally advanced or metastatic disease, with a 5-year survival rate of less than 5%. Although treatment options for these patients remain limited, drugs targeting the epidermal growth factor receptor (EGFR) have proved to be a highly effective therapy in NSCLC patients harboring sensitizing EGFR mutations.

Afatinib, a second-generation irreversible TKI, confers a theoretical advantage over re-versible TKIs in patients with acquired resistance. Through covalent binding to the kinase domain of EGFR, afatinib down regulates signaling from all homodimers and heter-odimers formed by ERBB receptor family members including EGFR, HER2 (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). HER2 mutations in NSCLC are rare, being found in approximately 1-4% of lung adenocarcinomas.

In contrast with reversible TKIs, the mechanisms of resistance to irreversible TKIs have not been fully elucidated, and identification of biomarkers that predict response to these drugs, particularly in patients progressing after first line therapy, is needed. In this study we assess the usefulness of plasma HGF concentrations as a predictor of response to afatinib in patients with advanced-stage lung adenocarcinoma.

Being tested
BIBW 2992
Keywords
Non-Small Cell Lung Cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BIBW 2992Drug

    Also called Afatinib

    All patients will receive: BIBW 2992 40mg every 24 hours orally, where a cycle corresponds to complete this treatment for 28 days; option 30mg/day dose reductions, according to established criteria.

    Not to be compared with any other drug.

Study groups in NCT01542437
Study groupRoleWhat they receive
BIBW 2992ExperimentalPatients received a daily oral 40mg dose of afatinib. Treatment was continued until docu-mented disease progression, unacceptable toxicity or withdrawal of consent. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 was used to evaluate toxicity. In patients with severe toxicity (grade ≥3) afatinib was temporary discontinued until the patient recovery to at least grade 1 toxicity and continued with a dose reduction to 30 mg/day. Dose reduction below 30mg/day was not allowed. Patients experiencing more than one grade ≥3 event, those with grade ≥2 toxicity after dose reduction, and/or those showing no recovery within 14 days discontinued treatment.
Receives: Drug: BIBW 2992

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response

    Is assigned to each subject the best objective response according to the investigator's decision (according to RECIST criteria). This is defined as the best response recorded from the start of treatment until progression / recurrence of disease. For patients with response status partial (PR) or complete response (CR), changes in tumor measurements must be confirmed by repeated assessments to be made not less than 4 weeks after it first reached the response criteria The CT will be made every two months to assess response to treatment. The objective response will be summarized descriptively.

    Measured: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died.

  2. Progression Free Survival

    Is defined as the time from start of treatment until the date of the first documented evidence of progression (RECIST criteria) or the date of death for any reason in the absence of disease progression (EP). For patients who have died or progressed at the time of final analysis, use the date of last contact.

    Measured: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died.

  3. Overall survival

    Overall survival will be determined from the date of commencement of treatment to date of death, regardless of the cause of death. In patients who did not die at the time of final analysis will use the date of last contact.

    Measured: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died.

Secondary outcomes (4)

  1. Evaluation of the HER-2 gene copy number and amplification

    Assessing the number of copies of the HER-2 gene by FISH

    Measured: Baseline

  2. DNA Extraction and Mutational Analysis of EGFR and HER-2

    Tumor samples were fixed in formalin and embedded in paraffin, used for histologic diagnosis of patients will be obtained from the Departments of Pathology participating institutes.

    Measured: Baseline

  3. Toxicity evaluation

    adverse effect from CTCAE

    Measured: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died.

  4. Determination of plasma HGF pre and post-treatment concentration

    Plasma samples were collected before the start of treatment with afatinib and after 2 months of treatment. HGF plasma levels were determined using ELISA, which was per-formed according to Quantikine human HGF immunoassay (DHG00; R\&D System, Minneapolis, MN, USA). All assays were performed in duplicate. Color intensity was measured at 450 nm with a spectrophotometric plate reader. HGF concentrations were determined by comparison with standard curves.

    Measured: Baseline and after 2 months of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionJun 2014
  4. Study completionJun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01542437
Sponsor's protocol ID
BIBW2992
Acronym
NSCLC
Status last verified
Feb 2024
First submitted
24 Feb 2012
Last updated
6 Feb 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Modjtahedi H, Dean C. The receptor for EGF and its ligands - expression, prognostic value and target for therapy in cancer (review). Int J Oncol. 1994 Feb;4(2):277-96. doi: 10.3892/ijo.4.2.277.

    PubMed 21566922

  • Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232. doi: 10.1016/1040-8428(94)00144-i. No abstract available.

    PubMed 7612182

  • Rusch V, Mendelsohn J, Dmitrovsky E. The epidermal growth factor receptor and its ligands as therapeutic targets in human tumors. Cytokine Growth Factor Rev. 1996 Aug;7(2):133-41. doi: 10.1016/1359-6101(96)00016-0.

    PubMed 8899291

  • Davies DE, Chamberlin SG. Targeting the epidermal growth factor receptor for therapy of carcinomas. Biochem Pharmacol. 1996 May 3;51(9):1101-10. doi: 10.1016/0006-2952(95)02232-5.

    PubMed 8645330

  • Veale D, Ashcroft T, Marsh C, Gibson GJ, Harris AL. Epidermal growth factor receptors in non-small cell lung cancer. Br J Cancer. 1987 May;55(5):513-6. doi: 10.1038/bjc.1987.104.

    PubMed 3038157

  • Sekine I, Takami S, Guang SG, Yokose T, Kodama T, Nishiwaki Y, Kinoshita M, Matsumoto H, Ogura T, Nagai K. Role of epidermal growth factor receptor overexpression, K-ras point mutation and c-myc amplification in the carcinogenesis of non-small cell lung cancer. Oncol Rep. 1998 Mar-Apr;5(2):351-4.

    PubMed 9468555

  • Pfeiffer P, Clausen PP, Andersen K, Rose C. Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections. Br J Cancer. 1996 Jul;74(1):86-91. doi: 10.1038/bjc.1996.320.

    PubMed 8679464

  • Cerny T, Barnes DM, Hasleton P, Barber PV, Healy K, Gullick W, Thatcher N. Expression of epidermal growth factor receptor (EGF-R) in human lung tumours. Br J Cancer. 1986 Aug;54(2):265-9. doi: 10.1038/bjc.1986.172.

    PubMed 3017396

  • Reissmann PT, Koga H, Figlin RA, Holmes EC, Slamon DJ. Amplification and overexpression of the cyclin D1 and epidermal growth factor receptor genes in non-small-cell lung cancer. Lung Cancer Study Group. J Cancer Res Clin Oncol. 1999;125(2):61-70. doi: 10.1007/s004320050243.

    PubMed 10190311

  • Fujino S, Enokibori T, Tezuka N, Asada Y, Inoue S, Kato H, Mori A. A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer. 1996 Nov;32A(12):2070-4. doi: 10.1016/s0959-8049(96)00243-2.

    PubMed 9014747

  • Fontanini G, Vignati S, Bigini D, Mussi A, Lucchi H, Angeletti CA, Pingitore R, Pepe S, Basolo F, Bevilacqua G. Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. Eur J Cancer. 1995;31A(2):178-83. doi: 10.1016/0959-8049(93)00421-m.

    PubMed 7718322

  • Rusch V, Baselga J, Cordon-Cardo C, Orazem J, Zaman M, Hoda S, McIntosh J, Kurie J, Dmitrovsky E. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer Res. 1993 May 15;53(10 Suppl):2379-85.

    PubMed 7683573

  • Ohsaki Y, Tanno S, Fujita Y, Toyoshima E, Fujiuchi S, Nishigaki Y, Ishida S, Nagase A, Miyokawa N, Hirata S, Kikuchi K. Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep. 2000 May-Jun;7(3):603-7. doi: 10.3892/or.7.3.603.

    PubMed 10767376

  • Lei W, Mayotte JE, Levitt ML. Enhancement of chemosensitivity and programmed cell death by tyrosine kinase inhibitors correlates with EGFR expression in non-small cell lung cancer cells. Anticancer Res. 1999 Jan-Feb;19(1A):221-8.

    PubMed 10226546

  • Veale D, Kerr N, Gibson GJ, Kelly PJ, Harris AL. The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br J Cancer. 1993 Jul;68(1):162-5. doi: 10.1038/bjc.1993.306.

    PubMed 8391303

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIBW 2992 in people with Non-Small Cell Lung Cancer and EGFR, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response (time frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01542437, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.

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