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

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

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.

Study Overview

• Status: Terminated
• Conditions: Lung Neoplasms
• Intervention / Treatment: Drug: BIBH 1

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 1998
• Primary Completion (ACTUAL): December 1, 2001

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (ESTIMATE): July 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: 1152.3