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Single Dose Escalation Study of 131I-Sibrotuzumab in Patients With Advanced or Metastatic Non-small Cell Lung Cancer

Phase 1
Terminated
Conditions
Carcinoma, Non-Small-Cell Lung
Interventions
Drug: 131I-Sibrotuzumab
Registration Number
NCT02209727
Lead Sponsor
Boehringer Ingelheim
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
9
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
131I-Sibrotuzumab131I-Sibrotuzumabsingle therapy dose administered over 60 minutes at week 4
Primary Outcome Measures
NameTimeMethod
Determination of the dose limiting toxicity (DLT)up to 12 weeks
Occurrence of toxicityup to 12 weeks

graded according to the Common Toxicity Criteria (CTC)

Determination of the maximum tolerated dose (MTD)up to 12 weeks

MTD is defined as the highest dose below which two patients experience DLT

Secondary Outcome Measures
NameTimeMethod
Maximum tumor response using the World Health Organisation (WHO) Disease Response Criteria8 weeks after therapeutic infusion
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