Dose-escalation Study of BIBH 1 in Patients With Non-small Cell Lung Cancer Scheduled for Surgical Resection

Study Overview
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Brief Summary
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Study to assess the toxicity, pharmacokinetics, biodistribution and imaging characteristics associated with increasing doses of 131I-BIBH 1, to compare the uptake of 131I-BIBH 1 in tumour to that of normal tissue in patients with non-small cell lung cancer and to measure human anti-human antibody (HAHA) concentrations.

Official Title
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A Phase I Single Dose-escalation Study of BIBH 1 in Patients With Non-small Cell Lung Cancer Scheduled for Surgical Resection

Conditions
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Lung Neoplasms

Intervention / Treatment
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* Drug: BIBH 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary or secondary advanced non-small cell lung cancer Eligible for a lung biopsy or scheduled for surgery that would provide biopsy material Karnofsky performance status of ≥ 70 Expected survival of ≥ 3 months Greater than or equal to 18 years of age Absolute granulocyte count ≥ 2.5 x 10**9/L Lymphocyte count > 0.7 x 10**9/L Platelet count ≥ 100 x 10**9/L Serum Creatinine ≤ 2.0 mg/dl (0.20 mmol/L) Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 3x upper limit of normal Total bilirubin < 2 mg/dl or 34µmol (SI unit equivalent) Ability to provide written informed consent Exclusion Criteria: Active metastatic disease to the central nervous system, exhibited by new or enlarging lesions on CT or MRI scan or within 3 months of treatment (i.e., surgery or radiotherapy) for brain metastases Exposure to an investigational agent within four weeks of the BIBH 1 infusion Patients that are not fully recovered from surgery. Because of the potential binding of BIBH 1 to healing scars, patients with incomplete healing at an incision site, as evidenced by incomplete granulation, infection or localized edema are excluded Chemotherapy or immunotherapy within four weeks preceding entry (six weeks for nitrsoureas and/or mitomycin-C.) Previous administration of a murine, chimeric or humanised measurement and/or antibody fragment Serious illness: e.g., active infections requiring antibiotics, bleeding disorders or diseases considered by the investigator to have potential for interfering with obtaining accurate results from this study Women who are breast-feeding or pregnant Men and women of childbearing potential who are unwilling to utilize a medically acceptable method of contraception Previous participation in this study Patients who have autoimmune disease or hypertopic skin conditions that possibly over-express Fibroblast Activation Protein and may be targeted by the antibody. These diseases include active inflammatory arthritis, cirrhosis and keloids. Patients with unstable angina pectoris. Patients prescribed medication to control their angina pectoris must be on a fixed dose for at least 1 month prior to screening to be eligible for the trial. Patients who experienced a myocardial infarction within 3 months of Screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBH 1<br>dose escalation: 0.5, 2, 10 or 20mg/m**2, 7 days prior to surgery | Drug: BIBH 1<br>* labeled with eight to ten millicurie of 131I<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of dose-limiting toxicities as defined by Common toxicity criteria (CTC) |  | up to 30 days | 
| Number of patients with abnormal biodistribution for 131I BIBH 1 |  | up to day 30 | 
| Tumor absorbed dose of 131I BIBH 1 |  | week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of human anti-human antibodies (HAHA) |  | up to day 30 |