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

NCT00748709 | Terminated Phase 2 Results

• 1 other identifier: 1200.26
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 15

Brief Summary

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Percentage of Participants With Clinical Benefit (CB)

  Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock

• Time to Objective Response (OR)

  Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock

• Duration of OR

  Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock.

• Progression-free Survival (PFS)

  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

  First administration of trial medication until 28 days after last administration of trial medication

Study Arms (1)

BIBW 2992 (Afatinib)

EXPERIMENTAL

BIBW 2992 (Afatinib) for patients FISH positive for/or harboring EGFR or HER2 Mutation

Drug: BIBW 2992 (Afatinib)

Interventions

BIBW 2992 (Afatinib) DRUG

BIBW 2992 (Afatininb) for patients FISH positive for/or harboring EGFR or HER2 Mutation

BIBW 2992 (Afatinib)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior treatment with gefitinib, erlotinib, lapatinib and/or other EGFR TKIs.
• 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)
• Inability to take BIBW 2992 by mouth (BIBW 2992 may not be crushed or administered via Gastrostomy-tube)
• Chronic diarrhea or other gastrointestinal disorders that may interfere with the absorption of the trial drug.
• 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).
• 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.
• 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.
• Active infectious disease
• Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with participation in this trial.
• 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.
• Absolute Neutrophil Count (ANC) less than 1,000/mm3.
• Platelet count less than 100,000/mm3.
• Hemoglobin Level less than 9.0 grams/dl.
• 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.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (15)

1200.26.3 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1200.26.11 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

Location

1200.26.9 Boehringer Ingelheim Investigational Site

Indianapolis, Indiana, United States

Location

1200.26.1 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Location

1200.26.13 Boehringer Ingelheim Investigational Site

Las Vegas, Nevada, United States

Location

1200.26.4 Boehringer Ingelheim Investigational Site

Albany, New York, United States

Location

1200.26.2 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1200.26.7 Boehringer Ingelheim Investigational Site

Kettering, Ohio, United States

Location

1200.26.12 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Location

1200.26.8 Boehringer Ingelheim Investigational Site

Tyler, Texas, United States

Location

1200.26.6 Boehringer Ingelheim Investigational Site

Norfolk, Virginia, United States

Location

1200.26.10 Boehringer Ingelheim Investigational Site

Vancouver, Washington, United States

Location

1200.26.88603 Boehringer Ingelheim Investigational Site

Tainan, Taiwan

Location

1200.26.88601 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1200.26.88602 Boehringer Ingelheim Investigational Site

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Due to early study termination, only data on the primary efficacy endpoint were summarized, no CIs were produced and efficacy and safety results were presented for the overall population rather than by tumor category.

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: September 8, 2008
• First Posted: September 9, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2010
• Last Updated: February 11, 2025
• Results First Posted: October 14, 2013

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (3); US (12)