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

NCT00879866 | Completed Phase 1

• 1 other identifier: EMR 62235-002
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Lung Cancer; Non Small Cell Lung Cancer

Keywords

NSCLC; immunocytokine; radiation; interleukin-2; immunotherapy; maintenance therapy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (7)

• Evaluate the pharmacokinetics (PK) of EMD 521873 in combination with local tumor irradiation

  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

  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

  First 4 cycles of treatment

• Collect evidence of best overall response after second-line therapy and duration of the response when it is shown

  At one year of follow up

• Evaluate progression-free survival and overall survival

  At one year of follow up

Study Arms (1)

1

EXPERIMENTAL

Biological: EMD 521873

Interventions

EMD 521873 BIOLOGICAL

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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (3)

Department of Thoracic Oncology, Netherlands Cancer Instiute - Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands

Location

Department of Pulmonology, Academic Hosptial Maastricht

Masstricht, Netherlands

Location

Department of Medical Oncology (452), Radboud UMC Nijmegen

Nijmegen, Netherlands

Location

Related Publications (2)

• Hendriks L, Dingemans AM, Lammens M, Anten MM, van den Heuvel MM, Postma LA. An Uncommon Presentation of Brain Metastases in a Lung Cancer Patient. J Thorac Oncol. 2015 Nov;10(11):1655-6. doi: 10.1097/JTO.0000000000000602. No abstract available.

  PMID: 26536198 DERIVED

• van den Heuvel MM, Verheij M, Boshuizen R, Belderbos J, Dingemans AM, De Ruysscher D, Laurent J, Tighe R, Haanen J, Quaratino S. NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy. J Transl Med. 2015 Jan 27;13:32. doi: 10.1186/s12967-015-0397-0.

  PMID: 25622640 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

EMD 521873

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Sonia Quaratino, MD, PhD

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2009
• First Posted: April 13, 2009
• Study Start: April 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: September 1, 2012
• Last Updated: June 23, 2014

Record last verified: 2014-06

Locations

NL (3)