EMD 521873 Plus Radiotherapy in Non Small Cell Lung Cancer (NSCLC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00879866
First received: April 10, 2009
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Non Small Cell Lung Cancer
Biological: EMD 521873
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the pharmacokinetics (PK) of EMD 521873 in combination with local tumor irradiation [ Time Frame: First 4 cycles of treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Evaluate progression-free survival and overall survival [ Time Frame: At one year of follow up ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: April 2009
Study Completion Date: September 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed NSCLC stage IIIb with malignant pleural effusion or stage IV
  • Pulmonary primary tumor or at least one NSCLC metastasis in the lung measuring at least 1 cm in diameter and eligible for local radiation with 20 Gy
  • Disease control (partial remission or stable disease) after 4 cycles of platinum-based first-line chemotherapy whereby the time between the last dose of first-line chemotherapy and start of trial treatment should not be longer than 8 weeks
  • Male or female, aged ≥18 years of age
  • Signed written informed consent
  • Effective contraception for male and female subjects of childbearing age
  • ECOG performance status 0 or 1
  • Adequate hematological function defined by WBC ≥3 x 10^9/L, neutrophils ≥1.5 x 10^9/L, lymphocyte count ≥0.5 x 10^9/L, platelet count ≥100 x 10^9/L; hemoglobin ≥9 g/dL
  • Estimated creatinine clearance ≥50 mL/min according to the Cockcroft - Gault formula or 24-h urine sampling
  • Adequate hepatic function defined by a total bilirubin level ≤1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 x ULN

Exclusion Criteria:

  • Requirement for immunosuppressive treatment with the exception of inhalative corticosteroids or low-dose systemic corticosteroids (prednisone equivalent dose ≤10 mg/day)
  • Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis)
  • Organ transplant recipients
  • Active infections (including HIV, hepatitis B and C, tuberculosis)
  • Known or clinically suspected brain metastases
  • Active cardiovascular/cerebrovascular disease (e.g. symptomatic coronary vascular disease, congestive heart failure ≥ NYHA II, LVEF <50%, ventricular arrhythmia requiring medication, myocardial infarction or stroke) within previous 6 months
  • Pericardial effusion
  • Major impairment in pulmonary function: forced expir¬atory volume in 1 second (FEV1) <50% and diffusion capacity for carbon monoxide (DLCO) <50% of normal limit
  • Any other significant disease that in the Investigator's opinion would exclude the subject from the trial
  • Known conditions associated with necroses of non-tumor bearing tissues (e.g. esophageal or gastroduodenal ulcers, ischemic bowel disease, chronic inflammations)
  • Pregnancy or lactation
  • Radiotherapy, chemotherapy, major surgery, biological therapy or any investigational drug within 30 days prior to the start of trial treatment
  • Requirement for concurrent systemic anticancer treatment (chemotherapy, biological therapy)
  • Pretreatment with anti-EGFR antibodies or tyrosine kinase inhibitors
  • Participation in another interventional clinical trial within the past 30 days before start of trial treatment
  • Known alcohol or drug abuse
  • Any psychiatric condition that would prohibit the understanding or rendering of the informed consent
  • Legal incapacity or limited legal capacity
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00879866

Locations
Netherlands
Department of Thoracic Oncology, Netherlands Cancer Instiute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands
Department of Pulmonology, Academic Hosptial Maastricht
Masstricht, Netherlands
Department of Medical Oncology (452), Radboud UMC Nijmegen
Nijmegen, Netherlands
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Sonia Quaratino, MD, PhD Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00879866     History of Changes
Other Study ID Numbers: EMR 62235-002
Study First Received: April 10, 2009
Last Updated: June 20, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Merck KGaA:
NSCLC
immunocytokine
radiation
interleukin-2
immunotherapy
maintenance therapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Pleural Effusion, Malignant
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pleural Neoplasms
Pleural Effusion
Pleural Diseases

ClinicalTrials.gov processed this record on July 29, 2014