Clinical trial NCT01015443: Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Carcinoma
Tecemotide
L-BLP25
Cyclophosphamide
placebo controlled
Non-Small Cell Lung Cancer
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-11-18
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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

Primary outcomes:
measure: Overall Survival (OS) Time
timeFrame: From the date of randomization until death, assessed up to 5.6 years
Secondary outcomes:
measure: Time to Symptom Progression (TTSP)
timeFrame: From the date of randomization to the date of symptomatic progression, assessed up to 5.6 years
measure: Time to Progression (TTP)
timeFrame: From the date of randomization to the date of radiological confirmation of PD, assessed up to 5.6 years
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization to PD, assessed up to 5.6 years
measure: Time to Treatment Failure (TTF)
timeFrame: From the date of randomization to the date of first missed treatment, assessed up to 5.6 years
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: 307 Hospital of Chinese PLA
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Beijing
country: China
facility: Cancer Institue & Hospital, Chinese Academy of Medical Sciences
city: ChangChun
country: China
facility: The First Hospital of Jilin University
city: Changchun
country: China
facility: Jillin Provincial Cancer Hospital
city: Chengdu, Sichuan Province
country: China
facility: West China Hospital of Sichuan University
city: Chongqing
country: China
facility: Southwest Hospital of the Third Military Medical University
city: Chongqing
country: China
facility: The Second Affiliate Hospital of the Third Military Medical University
city: Fuzhou
country: China
facility: Fujian Province Tumor Hospital
city: GuangZhou
country: China
facility: Guangdong General Hospital
city: Guangzhou
country: China
facility: The First Affilated Hospital of Guangzhou Medical College
city: Haerbin
country: China
facility: Heilongjiang Cancer Hospital
city: Haidian Districk, Beijing
country: China
facility: China PLA General Hospital
city: Hangzhou, Zhejiang
country: China
facility: Sir Run Run Shaw Hospital
city: Hangzhou, Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Kunming
country: China
facility: Yunan Tumor Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing, Jiangsu
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: PLA 81 Hospital
city: Shanghai
country: China
facility: Fundan University Cancer Hospital
city: Shanghai
country: China
facility: Shangahi Pulmonary Hosptial
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hosptial
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical Colleague of Huazhong University of Science and Technology
city: XiCheng District, Beijing
country: China
facility: Peking Union Medical College Hospital
city: Yangzhou
country: China
facility: Subei People's Hospital
city: Kowloon
country: Hong Kong
facility: Queen Elizabeth Hospital
city: New Territories
country: Hong Kong
facility: Tuen Mun Hospital
city: Pok Fu Lam
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin, N.T.
country: Hong Kong
facility: Prince of Wales Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsi University College of Medicine
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital, The Catholic University of Korea
city: Singapore
country: Singapore
facility: National University Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung County
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan County
country: Taiwan
facility: Chi Mei Hospital, Liouying
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital, Dept of Chest
city: Tao-Yuan
country: Taiwan
facility: Chang Gung medical Foundation, Linkou Branch
Study officials:
affiliation: Merck Serono (Beijing), Pharmaceutical R&D Co., Ltd., an Affiliate of Merck KGaA Darmstadt, Germany
name: Medical responsible
role: STUDY_DIRECTOR
References:
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.
citation: Wu YL, Park K, Soo RA, Sun Y, Tyroller K, Wages D, Ely G, Yang JC, Mok T. INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer. BMC Cancer. 2011 Oct 7;11:430. doi: 10.1186/1471-2407-11-430.