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

June 20, 2014 updated by: Merck KGaA, Darmstadt, Germany

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Department of Thoracic Oncology, Netherlands Cancer Instiute - Antoni van Leeuwenhoek Hospital
      • Masstricht, Netherlands
        • Department of Pulmonology, Academic Hosptial Maastricht
      • Nijmegen, Netherlands
        • Department of Medical Oncology (452), Radboud UMC Nijmegen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Incidence of DLTs occurring during the first cycle (21 days) of administration of any dose of EMD 521873 following radiotherapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluate the pharmacokinetics (PK) of EMD 521873 in combination with local tumor irradiation
Time Frame: First 4 cycles of treatment
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
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
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
At one year of follow up
Evaluate progression-free survival and overall survival
Time Frame: At one year of follow up
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
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
First 4 cycles of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Sonia Quaratino, MD, PhD, Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (ACTUAL)

February 1, 2011

Study Completion (ACTUAL)

September 1, 2012

Study Registration Dates

First Submitted

April 10, 2009

First Submitted That Met QC Criteria

April 10, 2009

First Posted (ESTIMATE)

April 13, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 23, 2014

Last Update Submitted That Met QC Criteria

June 20, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMR 62235-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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