search
Back to results

Study of Tecemotide (L-BLP25) in Participants With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy

Primary Purpose

Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Tecemotide (L-BLP25)
Single low dose cyclophosphamide
Placebo
Saline
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring NSCLC, Stage III, EMD531444, L-BLP25, Cyclophosphamide, Immunotherapy, Tecemotide

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than or equal to (>=) 50 Gray (Gy). Participant must have completed the primary thoracic chemoradiotherapy at least 4 weeks and no later than 12 weeks prior to randomization
  • Written informed consent given before any study-related activities are carried out.
  • Histologically or cytologically documented unresectable stage III NSCLC. Cancer stage must be confirmed and documented by Computed Tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scan
  • Documented stable disease or objective response, according to RECIST, after primary chemoradiotherapy for unresectable stage III disease, within four weeks prior to randomization
  • Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >= 50 Gy
  • Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate bone marrow function
  • Greater than or equal to 20 years of age

Exclusion Criteria:

  • Lung cancer-specific therapy (including surgery), other than primary chemoradiotherapy. Note: exploratory surgery before study entry is allowed
  • Immunotherapy (e.g., interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) received within four weeks prior to randomization
  • Malignant pleural/pericardial effusion or pleural dissemination or separate tumor nodules in the same lobe at initial diagnosis and/or at study entry
  • Past or current history of neoplasm other than lung carcinoma, except for adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least five years
  • Autoimmune disease
  • A recognized immunodeficiency disease including cellular immunodeficiencies, hypogamma-globulinemia, or dysgammaglobulinemia; participants who have hereditary or congenital/acquired immunodeficiencies
  • Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy, including presence of diffuse radiation pneumonitis spreading out of the involved field
  • Known Hepatitis B and/or C
  • Clinically significant hepatic dysfunction
  • Clinically significant renal dysfunction
  • Clinically significant cardiac disease
  • Splenectomy
  • Infectious process that, in the opinion of the investigator, could compromise the subject's ability to mount an immune response
  • Pregnant or breast-feeding women. Participants whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard. Male and female subjects who have a reproductive ability, unless using effective contraception as determined by the investigator throughout the study until at least 6 months after the last study treatment
  • Known drug abuse or alcohol abuse
  • Legal incapacity or limited legal capacity

Sites / Locations

  • Please contact the Merck KGaA Communication Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tecemotide (L-BLP25) + Cyclophosphamide

Placebo + Saline

Arm Description

Active

Control

Outcomes

Primary Outcome Measures

Overall Survival (OS) Time
OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date (01 May 2014), whichever was earlier.

Secondary Outcome Measures

Time To Progression (TTP) - Investigator Read
TTP was defined as the time from date of randomization to date of radiological diagnosis of PD (based on Response Evaluation Criteria in Solid Tumors [RECIST] v1.0). In the event that radiological confirmation could not be obtained but participant was withdrawn from trial treatment or died due to disease progression, TTP was measured from date of randomization to the date of discontinuation of trial treatment. Participants without event who died from causes other than disease progression were censored at date of death. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration. Participants without event with ongoing treatment at time of analysis, or who had stopped treatment for reasons other than PD, were censored on the date of last treatment administration.
Progression Free Survival (PFS) Time - Investigator Read
PFS time was defined as the duration from randomization to either first observation of objective PD (based on RECIST v1.0) or occurrence of death due to any cause. Participants without event still on treatment at time of analysis, or who stopped treatment for reasons other than PD or PD without radiological confirmed progression, were censored at the last imaging date. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration.
Time to Treatment Failure (TTF)
TTF was defined as the duration from date of randomization to the date of discontinuation of any trial treatment (cyclophosphamide or saline, tecemotide [L-BLP25] or placebo vaccine) for any reason as reported by the Investigator. Participants who had missed 2 consecutive scheduled doses and were subsequently lost to follow-up were considered as treatment failures with event date as date of first missed administration. Participants without event still on treatment at time of analysis were censored on the date of last treatment administration.

Full Information

First Posted
August 5, 2009
Last Updated
September 21, 2015
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., Japan
search

1. Study Identification

Unique Protocol Identification Number
NCT00960115
Brief Title
Study of Tecemotide (L-BLP25) in Participants With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy
Official Title
Combined Phase I/II Clinical Study of EMD531444(L-BLP25 or BLP25 Liposome Vaccine) in Subjects With Stage III Unresectable Non-small Cell Lung Cancer Following Primary Chemoradiotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., Japan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase I/II study in Japan to evaluate the safety of EMD531444 and its effects on survival time in patients with stage III unresectable non-small cell lung cancer.
Detailed Description
Phase I part is designed to evaluate the safety of EMD531444 930 microgram (mcg) dose to be used in phase II. Phase II part is designed to be conducted as randomized, double blind, placebo controlled study to compare overall survival time in all randomized subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
NSCLC, Stage III, EMD531444, L-BLP25, Cyclophosphamide, Immunotherapy, Tecemotide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tecemotide (L-BLP25) + Cyclophosphamide
Arm Type
Experimental
Arm Description
Active
Arm Title
Placebo + Saline
Arm Type
Placebo Comparator
Arm Description
Control
Intervention Type
Biological
Intervention Name(s)
Tecemotide (L-BLP25)
Other Intervention Name(s)
EMD531444, L-BLP25, BLP25 Liposome Vaccine
Intervention Description
After receiving a single low-dose cyclophosphamide, participants will receive weekly subcutaneous vaccinations with tecemotide (L-BLP25) (930 microgram [mcg]) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (930 mcg) will be administered every 6 weeks until progressive disease (PD).
Intervention Type
Drug
Intervention Name(s)
Single low dose cyclophosphamide
Intervention Description
A single intravenous (IV) infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg/m^2) of cyclophosphamide will be administered 3 days prior to tecemotide (L-BLP25), the first vaccine treatment.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
After receiving single dose of saline, participants will receive weekly subcutaneous vaccinations with placebo that matches with tecemotide (L-BLP25) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with placebo will be administered every 6 weeks until PD.
Intervention Type
Other
Intervention Name(s)
Saline
Intervention Description
A single dose of saline (sodium chloride, 9 grams per liter [g/L]) will be administered intravenously, 3 days prior to the start of placebo.
Primary Outcome Measure Information:
Title
Overall Survival (OS) Time
Description
OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date (01 May 2014), whichever was earlier.
Time Frame
Time from randomization to death or last day known to be alive reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).
Secondary Outcome Measure Information:
Title
Time To Progression (TTP) - Investigator Read
Description
TTP was defined as the time from date of randomization to date of radiological diagnosis of PD (based on Response Evaluation Criteria in Solid Tumors [RECIST] v1.0). In the event that radiological confirmation could not be obtained but participant was withdrawn from trial treatment or died due to disease progression, TTP was measured from date of randomization to the date of discontinuation of trial treatment. Participants without event who died from causes other than disease progression were censored at date of death. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration. Participants without event with ongoing treatment at time of analysis, or who had stopped treatment for reasons other than PD, were censored on the date of last treatment administration.
Time Frame
Time from randomization to PD, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).
Title
Progression Free Survival (PFS) Time - Investigator Read
Description
PFS time was defined as the duration from randomization to either first observation of objective PD (based on RECIST v1.0) or occurrence of death due to any cause. Participants without event still on treatment at time of analysis, or who stopped treatment for reasons other than PD or PD without radiological confirmed progression, were censored at the last imaging date. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration.
Time Frame
Time from randomization to disease progression, death or last tumor assessment, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).
Title
Time to Treatment Failure (TTF)
Description
TTF was defined as the duration from date of randomization to the date of discontinuation of any trial treatment (cyclophosphamide or saline, tecemotide [L-BLP25] or placebo vaccine) for any reason as reported by the Investigator. Participants who had missed 2 consecutive scheduled doses and were subsequently lost to follow-up were considered as treatment failures with event date as date of first missed administration. Participants without event still on treatment at time of analysis were censored on the date of last treatment administration.
Time Frame
Time from randomization to discontinuation of trial treatment, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than or equal to (>=) 50 Gray (Gy). Participant must have completed the primary thoracic chemoradiotherapy at least 4 weeks and no later than 12 weeks prior to randomization Written informed consent given before any study-related activities are carried out. Histologically or cytologically documented unresectable stage III NSCLC. Cancer stage must be confirmed and documented by Computed Tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scan Documented stable disease or objective response, according to RECIST, after primary chemoradiotherapy for unresectable stage III disease, within four weeks prior to randomization Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >= 50 Gy Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate bone marrow function Greater than or equal to 20 years of age Exclusion Criteria: Lung cancer-specific therapy (including surgery), other than primary chemoradiotherapy. Note: exploratory surgery before study entry is allowed Immunotherapy (e.g., interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) received within four weeks prior to randomization Malignant pleural/pericardial effusion or pleural dissemination or separate tumor nodules in the same lobe at initial diagnosis and/or at study entry Past or current history of neoplasm other than lung carcinoma, except for adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least five years Autoimmune disease A recognized immunodeficiency disease including cellular immunodeficiencies, hypogamma-globulinemia, or dysgammaglobulinemia; participants who have hereditary or congenital/acquired immunodeficiencies Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy, including presence of diffuse radiation pneumonitis spreading out of the involved field Known Hepatitis B and/or C Clinically significant hepatic dysfunction Clinically significant renal dysfunction Clinically significant cardiac disease Splenectomy Infectious process that, in the opinion of the investigator, could compromise the subject's ability to mount an immune response Pregnant or breast-feeding women. Participants whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard. Male and female subjects who have a reproductive ability, unless using effective contraception as determined by the investigator throughout the study until at least 6 months after the last study treatment Known drug abuse or alcohol abuse Legal incapacity or limited legal capacity
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Please contact the Merck KGaA Communication Center
City
Darmstadt
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
34870327
Citation
Zhu J, Yuan Y, Wan X, Yin D, Li R, Chen W, Suo C, Song H. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst Rev. 2021 Dec 6;12(12):CD011300. doi: 10.1002/14651858.CD011300.pub3.
Results Reference
derived

Learn more about this trial

Study of Tecemotide (L-BLP25) in Participants With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy

We'll reach out to this number within 24 hrs