Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
Study to determine the maximum tolerated dose (MTD) and safety profile of a single-dose administration of sibrotuzumab (50 mg) conjugated to an increasing dose of 131 I isotope.
Interventions
DRUG131I-Sibrotuzumab
50 mg Sibrotuzumab conjugated with 131I
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of advanced, non-resectable, and/or metastatic non-small cell lung cancer and at least one previous conventional treatment for advanced disease * Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable or evaluable disease, determined by World Health Organization (WHO) criteria using standard imaging modalities, including ultrasound, X-ray, CT and/or Magnetic Resonance Imaging (MRI). Bone scans and/or antibody scans are not to be used to determine the extent of the disease * Expected survival of ≥ 16 weeks * At least 18 years of age * Platelet count ≥ 100 x 10\*\*9/L * Absolute neutrophil count ≥ 2.0 x 10\*\*9/L * Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal or \< 5 x upper limit of normal if liver metastases are present * Total bilirubin ≤ 2mg/dL * Serum creatinine ≤ 2mg/dL * Ability to provide written informed consent
Exclusion criteria
* Known brain metastases * Exposure to an investigational agent within 30 days prior to receiving the scout dose * Incomplete recovery from surgery or incomplete healing of an incision site or evidence of infection * Treatment with cytotoxic chemotherapy, radiation or immunosuppressive therapy within the 30 days (42 days for nitrosoureas and/or mitomycin C) of the scout infusion. Patients using inhaled corticosteroids are considered eligible for enrollment * Serious illnesses, i.e., active infections requiring antibiotics, bleeding disorders or other serious illnesses precluding the use of either 131I or sibrotuzumab * Women who are breast-feeding or pregnant * Men and women who were sexually active and are unwilling to utilize a medically acceptable method of contraception * Hypertrophic skin disease or autoimmune disease that possibly involves over-expression of fibroblast activation protein (FAP), which can be targeted by the antibody. These diseases include active inflammatory arthritis, cirrhosis, and keloids * Unstable angina pectoris. Patients prescribed medication to control their angina pectoris must have been on a fixed dose for at least 1 month prior to screening to be eligible for trial enrollment * Myocardial infarction within 3 months prior to screening * New York Heart Association (NYHA) Heart failure stage III or IV, or a left ventricular ejection fraction of ≤ 40 % * Impaired lung function, measured by a decrease in forced expiratory volume at one second (FEV1) to less than 50 % of the predicted normal value
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the dose limiting toxicity (DLT) | up to 12 weeks | — |
| Determination of the maximum tolerated dose (MTD) | up to 12 weeks | MTD is defined as the highest dose below which two patients experience DLT |
| Occurrence of toxicity | up to 12 weeks | graded according to the Common Toxicity Criteria (CTC) |
Secondary
| Measure | Time frame |
|---|---|
| Maximum tumor response using the World Health Organisation (WHO) Disease Response Criteria | 8 weeks after therapeutic infusion |
Outcome results
None listed