Lung CancerPhase 1NCT00879866
EMD 521873 Plus Radiotherapy in Non Small Cell Lung Cancer (NSCLC)
A Phase 1 study testing EMD 521873 in people with Lung Cancer and Non Small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Non Small Cell Lung Cancer
- What is being tested?
- EMD 521873
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesNetherlands
- Study dates
- Apr 2009to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Department of Thoracic Oncology, Netherlands Cancer Instiute - Antoni van Leeuwenhoek Hospital
Amsterdam
Department of Pulmonology, Academic Hosptial Maastricht
Masstricht
Department of Medical Oncology (452), Radboud UMC Nijmegen
Nijmegen
About this study
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
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
- Being tested
- EMD 521873
- Keywords
- NSCLC, immunocytokine, radiation, interleukin-2, immunotherapy, maintenance therapy
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMD 521873Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Biological: EMD 521873 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: First 4 cycles of treatment
Collect evidence of best overall response after second-line therapy and duration of the response when it is shown
Measured: At one year of follow up
Evaluate progression-free survival and overall survival
Measured: 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
Measured: 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)
Measured: First 4 cycles of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2009 (estimated)
- Study startApr 2009
- Primary completionFeb 2011
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sonia Quaratino, MD, PhD, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00879866
- Sponsor's protocol ID
- EMR 62235-002
- Status last verified
- Jun 2014
- First submitted
- 10 Apr 2009
- Last updated
- 23 Jun 2014
- Results posted
- No
Publications
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.
PubMed 26536198van 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.
PubMed 25622640
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00879866
- Acronym / sponsor ID
- EMR 62235-002
- Conditions
- Lung Cancer, Non Small Cell Lung Cancer
- Keywords
- NSCLC, immunocytokine, radiation, interleukin-2, immunotherapy, maintenance therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Feb 2011 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 13 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: EMD 521873 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMD 521873After 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. | Biological | 1 |
Primary outcome
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
7 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2014.
- Derived from this study: PubMed 26536198Hendriks 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.
- Derived from this study: PubMed 25622640van 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.
Related trials for Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonia Quaratino, MD, PhD study director
Merck KGaA, Darmstadt, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EMD 521873 in people with Lung Cancer and Non Small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00879866, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2014.