EMD 521873 Plus Radiotherapy in Non Small Cell Lung Cancer (NSCLC)
Primary trial objective in this single arm trial is to assess the safety and tolerability of Selectikine (EMD 521873) given in combination with and local tumor irradiation and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 0.45 mg/kg.
Secondary objectives are to evaluate PK, immunogenicity, overall response, changes in tumor marker levels and circulating tumor cell numbers, progression-free survival and overall survival. Also, to evaluate biological/immune responses to EMD 521873.
NSCLC patients have to be stable (PR or SD) after first-line chemotherapy in order to be enrolled. A total of 12 to 24 patients are planned. Patients will remain on the dose throughout the trial. It is intended to administer at least 4 cycles (21 d each), or until progression or 2nd line therapy becomes necessary.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Phase Ib, Dose-escalation Trial on the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Biological Effects and Antitumor Activity of EMD 521873 in Combination With Local Irradiation (20 Gy) of Primary Tumors or Metastases in Subjects With Non-small Cell Lung Cancer Stage IIIb With Malignant Pleural Effusion or Stage IV With Disease Control (Partial Response or Stable Disease) After Application of 4 Cycles of Platinum-based, First-line Chemotherapy|
- To assess the safety and tolerability of EMD 521873 given in combination with local irradiation of pulmonary primary tumor/metastases and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 0.45 mg/kg. [ Time Frame: Incidence of DLTs occurring during the first cycle (21 days) of administration of any dose of EMD 521873 following radiotherapy ]
- Evaluate the pharmacokinetics (PK) of EMD 521873 in combination with local tumor irradiation [ Time Frame: First 4 cycles of treatment ]
- Evaluate the immunogenicity of EMD 521873 in combination with local tumor irradiation by measuring the induction of anti-EMD 521873 antibodies [ Time Frame: First 4 cycles of treatment in each cycle, then every 4 cycles ]
- Collect evidence of best overall response, changes in tumor marker levels and circulating tumor cell numbers after treatment with EMD 521873 in combination with local tumor irradiation [ Time Frame: First 4 cycles of treatment ]
- Collect evidence of best overall response after second-line therapy and duration of the response when it is shown [ Time Frame: At one year of follow up ]
- Evaluate progression-free survival and overall survival [ Time Frame: At one year of follow up ]
- Evaluate biological/immune responses following treatment with EMD 521873 by assessing changes in relevant parameters including leukocyte subset analysis [ Time Frame: First 4 cycles of treatment ]
- Evaluate biological/immune responses following treatment with EMD 521873 by assessing changes in relevant parameters including: molecular markers of immune activation (e.g. cytokines/chemokines, IL-2 receptor and neopterin) [ Time Frame: First 4 cycles of treatment ]
|Study Start Date:||April 2009|
|Study Completion Date:||September 2012|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Biological: EMD 521873
After local irradiation (5 x 4 Gy) given over 5 consecutive days and 2 treatment free days cohorts of 3-6 subjects will receive EMD 521873 (as a 1h-infusion) on 3 consecutive days in 3-week cycles at dose levels of 0.15, 0.30, and 0.45 mg/kg, respectively.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00879866
|Department of Thoracic Oncology, Netherlands Cancer Instiute - Antoni van Leeuwenhoek Hospital|
|Department of Pulmonology, Academic Hosptial Maastricht|
|Department of Medical Oncology (452), Radboud UMC Nijmegen|
|Study Director:||Sonia Quaratino, MD, PhD||Merck KGaA|