Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Biological: TecemotideDrug: PlaceboOther: SalineOther: Best Supportive Care (BSC)
- Registration Number
- NCT01015443
- Lead Sponsor
- Merck KGaA, Darmstadt, Germany
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 285
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigational Arm Tecemotide Tecemotide (L-BLP25) + Single low dose cyclophosphamide + Best supportive care (BSC) Investigational Arm Single low dose cyclophosphamide Tecemotide (L-BLP25) + Single low dose cyclophosphamide + Best supportive care (BSC) Investigational Arm Best Supportive Care (BSC) Tecemotide (L-BLP25) + Single low dose cyclophosphamide + Best supportive care (BSC) Control Arm Placebo Saline + Placebo + Best supportive care (BSC) Control Arm Best Supportive Care (BSC) Saline + Placebo + Best supportive care (BSC) Control Arm Saline Saline + Placebo + Best supportive care (BSC)
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Time From the date of randomization until death, assessed up to 5.6 years 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
Name Time Method Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death 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 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.
Progression Free Survival (PFS) From the date of randomization to PD, assessed up to 5.6 years 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) From the date of randomization to the date of first missed treatment, assessed up to 5.6 years 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.
Time to Symptom Progression (TTSP) From the date of randomization to the date of symptomatic progression, assessed up to 5.6 years 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) From the date of randomization to the date of radiological confirmation of PD, assessed up to 5.6 years 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.
Trial Locations
- Locations (47)
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
Cancer Institue & Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, China
Southwest Hospital of the Third Military Medical University
🇨🇳Chongqing, China
The Second Affiliate Hospital of the Third Military Medical University
🇨🇳Chongqing, China
Guangdong General Hospital
🇨🇳GuangZhou, China
The First Affilated Hospital of Guangzhou Medical College
🇨🇳Guangzhou, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Shangahi Pulmonary Hosptial
🇨🇳Shanghai, China
Jillin Provincial Cancer Hospital
🇨🇳Changchun, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan Province, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Peking Union Medical College Hospital
🇨🇳XiCheng District, Beijing, China
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Tuen Mun Hospital
🇭🇰New Territories, Hong Kong
Severance Hospital, Yonsi University College of Medicine
🇰🇷Seoul, Korea, Republic of
Queen Mary Hospital
🇭🇰Pok Fu Lam, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, N.T., Hong Kong
National University Hospital
🇸🇬Singapore, Singapore
Subei People's Hospital
🇨🇳Yangzhou, China
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital, Dept of Chest
🇨🇳Taipei, Taiwan
Queen Elizabeth Hospital
🇭🇰Kowloon, Hong Kong
St. Mary's Hospital, The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
307 Hospital of Chinese PLA
🇨🇳Beijing, China
Beijing Chest Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳ChangChun, China
China PLA General Hospital
🇨🇳Haidian Districk, Beijing, China
Fujian Province Tumor Hospital
🇨🇳Fuzhou, China
Heilongjiang Cancer Hospital
🇨🇳Haerbin, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Yunan Tumor Hospital
🇨🇳Kunming, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Fundan University Cancer Hospital
🇨🇳Shanghai, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Shanghai Chest Hosptial
🇨🇳Shanghai, China
Tongji Hospital of Tongji Medical Colleague of Huazhong University of Science and Technology
🇨🇳Wuhan, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung medical Foundation, Linkou Branch
🇨🇳Tao-Yuan, Taiwan
PLA 81 Hospital
🇨🇳Nanjing, China