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Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population (INSPIRE)

This study has been terminated.
(The study is terminated prematurely as the sponsor decided to discontinue program with Tecemotide in NSCLC.)
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01015443
First received: October 1, 2009
Last updated: September 16, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of Asian subjects with unresectable stage III non-small cell lung cancer in comparison to a placebo plus best supportive care (a so-called placebo controlled study).

Condition Intervention Phase
Non-Small Cell Lung Cancer
Biological: Tecemotide
Drug: Single low dose cyclophosphamide
Drug: Placebo
Other: Saline
Other: Best Supportive Care (BSC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-national, Double-blind, Placebo-controlled, Randomized, Phase III Clinical Trial of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Asian Subjects With Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) Who Have Demonstrated Either Stable Disease or Objective Response Following Primary Chemo-radiotherapy

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Overall Survival (OS) Time [ Time Frame: From the date of randomization until death, assessed up to 5.6 years ] [ Designated as safety issue: No ]
    OS time was measured as the time (in months) between the date of randomization and the date of death. For subjects alive or lost to follow-up at time of analysis, the time between the date of randomization and the date on which the subject was last known alive was calculated and used as a censored observation in the analysis.


Secondary Outcome Measures:
  • Time to Symptom Progression (TTSP) [ Time Frame: From the date of randomization to the date of symptomatic progression, assessed up to 5.6 years ] [ Designated as safety issue: No ]
    TTSP was measured from randomization to symptomatic progression by lung cancer symptom scale (LCSS) used to measure symptom changes relevant to quality of life (QoL).It consisted of 9 items focused on cancer symptoms (loss of appetite, fatigue, cough, shortness of breath, blood in sputum, pain, symptoms of cancer, illness affecting normal activity, QoL).For each symptom score distance from left boundary to point where subject has marked line was measured in millimeters (mm).Total scale length was 100 mm. Symptomatic progression was defined as increase/worsening of average symptomatic burden index (ASBI) (mean of 6 major lung cancer specific symptom scores);Worsening defined as 10% increase of scale breadth from baseline. Score 0 indicate no/minimum symptoms;100 indicates maximum level of symptoms. Subjects without symptomatic progression/lost to follow-up at time of analysis: time from date of randomization to date of last LCSS assessment was calculated & used as censored observation.

  • Time to Progression (TTP) [ Time Frame: From the date of randomization to the date of radiological confirmation of PD, assessed up to 5.6 years ] [ Designated as safety issue: No ]
    Time from randomization to radiological confirmation of disease progression (PD) as determined by the investigator. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions from nadir, or the appearance of one or more new lesions as per RECIST version 1.0. For subjects without radiological confirmed PD who discontinued or died due to PD, the date of trial treatment discontinuation was used as event date. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered as having PD, TTP was calculated from the date of randomization to the date of their first missed treatment. Subjects without PD at time of analysis are censored at either date of last vaccination or death or discontinuation of treatment or lost to follow-up.

  • Progression Free Survival (PFS) [ Time Frame: From the date of randomization to PD, assessed up to 5.6 years ] [ Designated as safety issue: No ]
    Time from randomization to objective disease progression (PD) as determined by the investigator or death. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions from nadir, or the appearance of one or more new lesions as per RECIST version 1.0. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered as having PD, and the PFS was calculated from the date of randomization to the date of their first missed treatment. PFS time for subjects without an event was censored as of the date of last performed imaging.

  • Time to Treatment Failure (TTF) [ Time Frame: From the date of randomization to the date of first missed treatment, assessed up to 5.6 years ] [ Designated as safety issue: No ]
    TTF was time from randomization to discontinuation of trial treatment for any reason as reported by the investigator. For subjects still receiving treatment at the time of analysis, the time between the date of randomization and the last date of treatment will be used as a censored observation in the analysis. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered treatment failure and the TTF was calculated from the date of randomization to the date of their first missed treatment.

  • Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death [ Time Frame: From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years ] [ Designated as safety issue: Yes ]
    An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 42 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAE leading to death and permanent discontinuation of any trial treatment were presented.


Enrollment: 285
Study Start Date: December 2009
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Investigational Arm
Tecemotide (L-BLP25) + Single low dose cyclophosphamide + Best supportive care (BSC)
Biological: Tecemotide
Subjects will receive 8 consecutive weekly subcutaneous vaccinations with 918 microgram (mcg) of tecemotide (L-BLP25) at Week 1, 2, 3, 4, 5, 6, 7, and 8 (primary treatment phase) and then at 6-Week intervals, beginning at Week 14 (maintenance phase) until disease progression (PD) is documented or the subject discontinues for any other reason.
Other Names:
  • L-BLP25
  • Stimuvax
Drug: Single low dose cyclophosphamide
A single intravenous (IV) infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before the first administration of tecemotide.
Other: Best Supportive Care (BSC)
The BSC will be provided as per the investigator's discretion, and is not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Placebo Comparator: Control Arm
Saline + Placebo + Best supportive care (BSC)
Drug: Placebo
Subjects will receive 8 consecutive weekly subcutaneous vaccinations of tecemotide (L-BLP25) matching placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinues for any other reason.
Other: Saline
A single IV infusion of 0.9 percent (%) sodium chloride (saline) will be given 3 days before first placebo vaccination.
Other: Best Supportive Care (BSC)
The BSC will be provided as per the investigator's discretion, and is not limited to palliative radiation, psychosocial support, analgesics and nutritional support.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented unresectable stage III non-small cell lung cancer (NSCLC)
  • Documented stable disease or objective response, according to Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST v1.0) after primary concomitant chemo-radiotherapy for unresectable stage III disease, within four weeks (28 days) prior to randomization
  • Receipt of concomitant chemo-radiotherapy. The chemotherapy-part must have been platinum-based, must have been administered with a minimum of two cycles overlap with radiotherapy (one cycle lasts either 3 or 4 weeks depending on the chemotherapy regimen), and a minimum of two platinum-based chemotherapy administrations must have been given during radiotherapy. Purely radio sensitizing doses of chemotherapy are not acceptable. Radiotherapy must have delivered a radiation dose of >= (greater than or equal to) 50 Gray (Gy). Induction or consolidation chemotherapy is allowed and if given, should be accounted as part of primary thoracic chemoradiotherapy. Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible
  • Geographically accessible for ongoing follow-up, and committed to comply with the designated visits
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • A platelet count >= the lower limit of normal for the site or >= 100 x 10^9 per liter (/Liter) (whichever is greater); white blood cell (WBC) >= 2.5 x 10^9/Liter and haemoglobin >= 90 gram per liter (g/L)
  • >=18 years of age (or minimum age of legal consent consistent with local regulations, if minimum is greater than [>] 18 years of age)
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

Pre-Therapies*:

  • Prior sequential chemo-radiotherapy
  • Lung-cancer-specific therapy (including surgery) other than primary chemoradiotherapy
  • Immunotherapy (e.g., interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GMCSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within four weeks (28 days) prior to randomization
  • Investigational systemic drugs (including off-label use of approved products) within four weeks (28 days) prior to randomization

Disease Status:

  • Metastatic disease
  • Malignant pleural effusion at initial diagnosis and/or at trial entry
  • Past or current history of neoplasm other than lung carcinoma, except for curatively 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 5 years
  • Autoimmune disease
  • A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies
  • Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed)
  • Known active Hepatitis B infection and/or Hepatitis C infection
  • Signs and symptoms suggestive of transmissible spongiform encephalopathy, or of family members who suffer(ed) from such

Physiological Functions:

  • 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

Standard Safety:

  • Pregnant or breastfeeding women, women of childbearing potential, unless using effective contraception as determined by the investigator
  • Known drug abuse or alcohol abuse
  • Participation in another clinical trial (excluding purely observational studies) within the past 28 days
  • Requires concurrent treatment with a non-permitted drug
  • Known hypersensitivity to any of the trial treatment ingredients
  • Legal incapacity or limited legal capacity
  • Any other reason that, in the opinion of the investigator precludes the subject from participating in the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01015443

  Hide Study Locations
Locations
China
307 Hospital of Chinese PLA
Beijing, China
Beijing Cancer Hospital
Beijing, China
Beijing Chest Hospital
Beijing, China
Cancer Institue & Hospital, Chinese Academy of Medical Sciences
Beijing, China
The First Hospital of Jilin University
ChangChun, China, 130021
Jillin Provincial Cancer Hospital
Changchun, China
West China Hospital of Sichuan University
Chengdu, Sichuan Province, China
Southwest Hospital of the Third Military Medical University
Chongqing, China
The Second Affiliate Hospital of the Third Military Medical University
Chongqing, China
Fujian Province Tumor Hospital
Fuzhou, China
Guangdong General Hospital
GuangZhou, China
The First Affilated Hospital of Guangzhou Medical College
Guangzhou, China
Heilongjiang Cancer Hospital
Haerbin, China
China PLA General Hospital
Haidian Districk, Beijing, China
Sir Run Run Shaw Hospital
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
The First Affiliated Hospital of Anhui Medical University
Hefei, China
Yunan Tumor Hospital
Kunming, China
The First Affiliated Hospital of Nanchang University
Nanchang, China
Jiangsu Cancer Hospital
Nanjing, Jiangsu, China
PLA 81 Hospital
Nanjing, China
Fundan University Cancer Hospital
Shanghai, China
Shangahi Pulmonary Hosptial
Shanghai, China
Shanghai Chest Hospital
Shanghai, China
Shanghai Chest Hosptial
Shanghai, China
Cancer Hospital of Shantou University Medical College
Shantou, China
Tongji Hospital of Tongji Medical Colleague of Huazhong University of Science and Technology
Wuhan, China
Peking Union Medical College Hospital
XiCheng District, Beijing, China
Subei People's Hospital
Yangzhou, China
Hong Kong
Queen Elizabeth Hospital
Kowloon, Hong Kong
Tuen Mun Hospital
New Territories, Hong Kong
Queen Mary Hospital
Pok Fu Lam, Hong Kong
Prince of Wales Hospital
Shatin, N.T., Hong Kong
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Severance Hospital, Yonsi University College of Medicine
Seoul, Korea, Republic of
St. Mary's Hospital, The Catholic University of Korea
Seoul, Korea, Republic of
Singapore
National University Hospital
Singapore, Singapore
Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Chang Gung Medical Foundation, Kaohsiung
Kaohsiung County, Taiwan
China Medical University Hospital
Taichung City, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
Chi Mei Hospital, Liouying
Tainan County, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital, Dept of Chest
Taipei, Taiwan
Chang Gung medical Foundation, Linkou Branch
Tao-Yuan, Taiwan
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical responsible Merck Serono (Beijing), Pharmaceutical R&D Co., Ltd., an Affiliate of Merck KGaA Darmstadt, Germany
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01015443     History of Changes
Other Study ID Numbers: EMR63325-012 
Study First Received: October 1, 2009
Results First Received: June 17, 2016
Last Updated: September 16, 2016
Health Authority: China: Ministry of Health
China: Food and Drug Administration
Hong Kong: Department of Health
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs

Keywords provided by Merck KGaA:
Non-Small Cell Lung Carcinoma
Tecemotide
L-BLP25
Cyclophosphamide
placebo controlled
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on December 09, 2016