Phase II Trial of BIBW 2992 (Afatinib) in Genetically Pre-screened Cancers With EGFR and/or HER2 Gene Amplification.

An Open Label Phase II Trial of BIBW 2992 (Afatinib) in Genetically Pre-screened Cancers With EGFR and/or HER2 Gene Amplification or EFGR Activating Mutations.

This is a Phase II open-label exploratory trial of BIBW 2992 administered to patients with tumors of various histologies found to possess EGFR and/or HER2 gene amplification, or EGFR activating mutations.

Study Overview

• Status: Terminated
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BIBW 2992 (Afatinib)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • 1200.26.88603 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1200.26.88601 Boehringer Ingelheim Investigational Site
  • Tao-Yuan, Taiwan
    • 1200.26.88602 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Los Angeles, California, United States
      • 1200.26.3 Boehringer Ingelheim Investigational Site
  • Colorado
    • Denver, Colorado, United States
      • 1200.26.11 Boehringer Ingelheim Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States
      • 1200.26.9 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • 1200.26.1 Boehringer Ingelheim Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States
      • 1200.26.13 Boehringer Ingelheim Investigational Site
  • New York
    • Albany, New York, United States
      • 1200.26.4 Boehringer Ingelheim Investigational Site
    • New York, New York, United States
      • 1200.26.2 Boehringer Ingelheim Investigational Site
  • Ohio
    • Kettering, Ohio, United States
      • 1200.26.7 Boehringer Ingelheim Investigational Site
  • Texas
    • Dallas, Texas, United States
      • 1200.26.12 Boehringer Ingelheim Investigational Site
    • Tyler, Texas, United States
      • 1200.26.8 Boehringer Ingelheim Investigational Site
  • Virginia
    • Norfolk, Virginia, United States
      • 1200.26.6 Boehringer Ingelheim Investigational Site
  • Washington
    • Vancouver, Washington, United States
      • 1200.26.10 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

There are 2 Steps in the screening process:

Step 1 Inclusion criteria for pre-screening:

1. Histologically confirmed diagnosis of advanced cancer of one of the following four tumor type categories:

   Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological cancers

2. Measurable disease by RECIST criteria.
3. Willingness and ability to give written informed consents consistent with ICHGCP guidelines.
4. Life expectancy of at least three (3) months.
5. Eastern Cooperative Oncology Group performance score 0, 1 or 2.
6. Age >18 years.

Step 2 Inclusion criteria for enrollment:

Patients who have tested positive for FISH and are considered candidate for this trial must meet all of the following inclusion criteria:

1. Histologically confirmed diagnosis of advanced cancer of one of the following four tumor type categories:

   Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological cancers

2. Documented failure to respond or progression of underlying cancer after at least one line of prior chemotherapy.
3. EGFR and/or HER2 gene amplification by FISH testing or patients with tumors that harbor known activating EGFR mutations.
4. Measurable disease by RECIST criteria.
5. Willingness and ability to give written informed consents consistent with ICH-GCP guidelines.
6. Life expectancy of at least three (3) months.
7. Eastern Cooperative Oncology Group performance score 0, 1 or 2.
8. Age >18 years.

Exclusion criteria:

1. Prior treatment with gefitinib, erlotinib, lapatinib and/or other EGFR TKIs.
2. Treatment with cytotoxic anti-cancer-therapies or investigational drugs during the last four weeks prior to the first treatment with the trial drug. (a shorter duration may be considered for patients treated with oral, non cytotoxic drugs on an individual basis and upon discussion between the principal investigator and sponsor)
3. Inability to take BIBW 2992 by mouth (BIBW 2992 may not be crushed or administered via Gastrostomy-tube)
4. Chronic diarrhea or other gastrointestinal disorders that may interfere with the absorption of the trial drug.
5. History of other malignancies unless free of disease for at least 3 years (except for appropriately treated superficial non-melanoma skin cancer and surgically cured cervical cancer in situ).
6. 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. Myocardial infarction within 6 months prior to randomization.
7. Resting left ventricular ejection fraction <50% OR below the institution's lower limit of normal (if the institutions lower limit is above 50%), measured by MUGA scan or echocardiogram.
8. Active infectious disease
9. Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with participation in this trial.
10. Active/symptomatic brain metastases. Patients with a history of treated brain metastases must have stable or normal brain MRI scan at screening and be at least three months post-radiation or surgery for brain metastasis.
11. Absolute Neutrophil Count (ANC) less than 1,000/mm3.
12. Platelet count less than 100,000/mm3.
13. Hemoglobin Level less than 9.0 grams/dl.
14. Total Bilirubin greater than 1.5 mg/dl; higher Total Bilirubin values may be acceptable for patients with known Gilbert¿s disease, approval by the PI and sponsor will be necessary.
15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal; or 5 times the upper limit of normal in patients with neoplastic liver involvement.
16. Serum creatinine greater than 1.5 x upper limit of normal for the institution.
17. Patients who are sexually active and unwilling to use simultaneously two medically acceptable method of contraception, one of which being a barrier type method such as condom.
18. Pregnancy or breast-feeding.
19. Patients unable to comply with the protocol
20. Active alcohol and/or substance abuse.
21. Continuation of therapy-related toxicities from prior anti cancer therapies, prior surgery, of CTCAE Grade >=2 at the time of the first administration of the trial drug.
22. Patients with known pre-existing interstitial lung disease.
23. Requirement for treatment with any of the prohibited concomitant medications: additional experimental anti-cancer treatment and/or standard chemotherapy, immunotherapy, hormone treatment or radiotherapy; P-gp inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBW 2992 (Afatinib); BIBW 2992 (Afatinib) for patients FISH positive for/or harboring EGFR or HER2 Mutation	Drug: BIBW 2992 (Afatinib); BIBW 2992 (Afatininb) for patients FISH positive for/or harboring EGFR or HER2 Mutation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	OR is defined as the percentage of patients with complete response (CR) or partial response (PR) and was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).	Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks thereafter

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Benefit (CB)	CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST 1.0 criteria.	Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock
Time to Objective Response (OR)	The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST 1.0 criteria.	Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock
Duration of OR	Duration of OR was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented.	Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock.
Progression-free Survival (PFS)	PFS was defined as the time from the start of treatment to the occurrence of disease progression or death, whichever came first. Disease progression was assessed according to RECIST 1.0 criteria as well as by the investigators assessment, progression date recorded from post trial follow up or start of new anticancer treatment.	Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock.
Patients With AEs Resulting in Dose Reduction or Treatment Discontinuation	Patients with adverse events (AEs) resulting in dose reduction or treatment discontinuation	First administration of trial medication until 28 days after last administration of trial medication
Maximum CTCAE Grade	Patients with AEs by maximum Common Terminology Criteria for Adverse Events (CTCAE) grade	First administration of trial medication until 28 days after last administration of trial medication
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 15 (Cpre,ss,15) for Patients on 50mg on Day 15	Cpre,ss,15 represents the pre-dose concentration of afatinib in plasma at steady state on day 15 for patients on 50mg on day 15.	Day 15
Number of Patients With Diarrhea or Rash	Number of Patients with Diarrhea or Rash	First administration of trial medication until 28 days after last administration of trial medication

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2008
• Primary Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: September 8, 2008
• First Submitted That Met QC Criteria: September 8, 2008
• First Posted (Estimated): September 9, 2008

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency