A Phase II Trial of Afatinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus

February 7, 2019 updated by: Yonsei University

As a 2nd generation EGFR-TKI that irreversibly binds to EGFR receptors, afatinib showed the possibility of superior effects to 1st generation TKIs such as erlotinib and gefitinib. In a phase III study LUX-lung 3 in patients with EGFR mutation-positive non-small-cell lung cancer, afatinib monotherapy showed longer progression-free disease survival time of 11.1 months than that (6.9 months) of pemetrexed/cisplatin combination therapy. Based on such the results, it is currently recommended as the standard first-line treatment for EGFR mutation-positive lung cancer, and clinical studies are also being actively conducted in other types of carcinomas characterized by EGFR gene mutation and overexpression. Thirty (30) solid cancer patients were included in a phase I trial of afatinib, and of them, a patient with esophageal cancer had partial response. Taken together, based upon the results from clinical trials of afatinib conducted so far, 7 out of 15 esophageal cancer patients achieved clinical responses of 3 months or longer.

Hence, the overall results from previous studies of gefitinib and erlotinib as EGFR TKIs and our study of dacomitinib, as well as from preceding studies of afatinib - a 2nd generation EGFR TKI - suggest the possibility of an effective therapy in esophageal cancer characterized by well-known EGFR overexpression. In this phase II trial, afatinib shall be administered to patients with squamous cell carcinoma of esophagus to evaluate its effects and toxicity. Also, biomarkers to predict responses to afatinib shall be explored through further studies.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed squamous cell carcinoma of esophagus
  • Age ≥ 20
  • ECOG PS 0-2
  • Ineligibility for local therapy (surgery or radiotherapy)

  • Patients who have failed to respond to or receive a first-line, palliative platinum-based chemotherapy

    1. Allowed to enroll the patients who have developed the recurrent cancer within 6 months after definitive/neo-adjuvant/adjuvant platinum-based chemotherapy(± radiotherapy), by considering the prior therapy as first-line chemotherapy.
    2. Allowed to enroll the patients who cannot undergo platinum-based chemotherapy or concurrent chemo-radiotherapy due to concern for renal function deterioration and the patient intolerance, without prior chemotherapy history.
  • At least one bidimensionally measurable disease as defined by RECIST ver 1.1

  • Adequate organ function for treatment

    1. Absolute neutrophil count (ANC) >=1000 cells/mm3
    2. Platelets ≥ 100,000 cells/mm3
    3. Estimated creatinine clearance ≥50 mL/min, or serum creatinine <1.5 x institution upper limit of normal (ULN) using Cockcroft and Gault formulas
    4. Bilirubin ≤1.5 x ULN
    5. AST (SGOT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases)
    6. ALT (SGPT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases)
    7. 12-Lead electrocardiogram (ECG) with normal tracing or nonclinically significant changes that do not require medical intervention QTc interval ≤470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality
  • The patient who has signed the informed consent prior to conducting study related screening procedures, and who understands that the study may be discontinued at anytime without disadvantages

Exclusion Criteria:

  • Previous treatment with EGFR tyrosine kinase inhibitors
  • Chemotherapy , immunotherapy or investigational durg within 3 weeks of study entry
  • Any major operation or irradiation within 4 weeks of baseline disease assessment
  • Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
  • Patients who confirmed CNS metastasis must have completed any prior treatment for CNS metastasis and steroid therapy for brain metastasis should stopped more 1week and stabled before first dose of study treatment
  • Patients with known interstitial lung disease
  • Patients with uncontrolled or significant cardiovascular disease
  • Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, thyroid cancer, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry.
  • Pregnant or breast feeding women
  • Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: afatinib group
Drug: BIBW2992

International Nonproprietary Name (INN): BIBW 2992 Pharmacological dosage form: Film-coated tablet Supplier: Boehringer Ingelheim Pharma GmbH & Co. KG Unit content: 40 mg, 30 mg, 20 mg film-coated tablet (BIBW 2992 content in film-coated tablet is related with equivalent free base BIBW 2992.) Daily dose: 40 mg Dosing period: To be successively administered once daily until a disease will develop, an unacceptable adverse event will occur, or another reason requiring discontinuation of the study will occur; For administration, study treatment consists of periods(each 4 weeks(28 days)).

Route of administration: Orally (Take by swallowing) Dosage: Once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
response rate
Time Frame: every 8 weeks until 2 years
every 8 weeks until 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression free survival
Time Frame: 2 year
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Anticipated)

January 1, 2020

Study Completion (Anticipated)

January 1, 2020

Study Registration Dates

First Submitted

January 23, 2015

First Submitted That Met QC Criteria

January 28, 2015

First Posted (Estimate)

February 3, 2015

Study Record Updates

Last Update Posted (Actual)

February 11, 2019

Last Update Submitted That Met QC Criteria

February 7, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4-2014-0432

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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