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

Phase 1

Terminated

• Conditions: Lung Neoplasms
• Interventions: Drug: BIBH 1

• Registration Number: NCT02199886
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 1998-07
• Primary Completion: 2001-12
• Status Verified: 2014-07
• Study First Submitted: 2014-07-24
• Study First Submitted QC: 2014-07-24
• Last Update Submitted: 2014-07-24
• Study First Posted: 2014-07-25
• Last Update Posted: 2014-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIBH 1	BIBH 1	dose escalation: 0.5, 2, 10 or 20mg/m\*\*2, 7 days prior to surgery

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Concentration of human anti-human antibodies (HAHA)	up to day 30