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

Non-Small Cell Lung Cancer Clinical Trial

— INSPIRE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01015443
• Other study ID #: EMR63325-012
• Status: Terminated
• Phase: Phase 3
• First received: October 1, 2009
• Last updated: September 3, 2015
• Start date: December 2009
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of HealthChina: Food and Drug AdministrationHong Kong: Department of HealthSingapore: Health Sciences AuthoritySouth Korea: Korea Food and Drug Administration (KFDA)Taiwan: Department of HealthTaiwan: National Bureau of Controlled Drugs
• Study type: Interventional

Clinical Trial 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 patients with unresectable stage III non-small cell lung cancer in comparison to a placebo plus best supportive care (a so-called Placebo controlled study).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 285
• Est. completion date: July 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented unresectable stage III 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 radiosensitizing 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 greater than or equal to (>=) the lower limit of normal for the site or >= 100 x 10^9 per liter (/L) (whichever is greater); WBC >= 2.5 x 10^9/L 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 > 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 that in the opinion of the investigator could compromise the safety of the subject in this trial

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Biological:
• Tecemotide (L-BLP25)
All subjects randomized to the investigational arm will begin the following treatment regimen within three days of randomization: A single I.V. infusion of 300 mg/m2 of cyclophosphamide administered exactly three days prior to the first Tecemotide (L-BLP25) vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with 918 µg Tecemotide (L-BLP25) at weeks 1, 2, 3, 4, 5, 6, 7, and 8 (primary treatment phase) and then at six-week intervals, beginning at week 14 (maintenance phase) and continuing until disease progression is documented or the subject discontinues for any other reason.
• Placebo
A single I.V. infusion of 0.9% sodium chloride will be administered to subjects randomized to the control arm exactly 3 days prior to treatment with placebo. Subjects will then receive eight consecutive weekly subcutaneous treatments with placebo at weeks 1, 2, 3, 4, 5, 6, 7, and 8 followed by maintenance treatment at 6 week intervals, beginning at week 14 and continuing until disease progression is documented.

Locations

Country	Name	City	State
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	Jillin Provincial Cancer Hospital	Changchun
China	The First Hospital of Jilin University	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	PLA 81 Hospital	Nanjing
China	Jiangsu Cancer Hospital	Nanjing, Jiangsu
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
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.
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
Singapore	National University Hospital	Singapore
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	Chang Gung Medical Foundation, Kaohsiung	Kaohsiung County
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	China Medical University Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chi Mei Hospital, Liouying	Tainan County
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital, Dept of Chest	Taipei
Taiwan	Chang Gung medical Foundation, Linkou Branch	Tao-Yuan

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

China,  Hong Kong,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Time	Time from randomization to death. Patients without event are censored at the date of last contact, or date lost to follow-up	From first participant randomised up to 5 years	No
Secondary	Time to Symptom Progression (TTSP)	Time from randomization to symptomatic progression. Symptomatic progression is defined as an increase (worsening) of the ASBI (The Average Symptomatic Burden Index i.e., the mean of the six major lung cancer specific symptom scores of the LCSS subject scale). Worsening is defined as a 10% increase in the scale breadth from the baseline score.	From first participant randomised up to 5 years	No
Secondary	Time to Progression (TTP)	Time from randomization to the radiological confirmation of progression performed according to Response Evaluation Criteria In Solid Tumors (RECIST). If radiological confirmation cannot be obtained but a subject is withdrawn from trial treatment due to PD, TTP will be measured from the date of randomization to the date of discontinuation of trial treatment. TTP of subjects without PD at the time of analysis will be censored at the time of last contact.	From first participant randomised up to 5 years	No
Secondary	Progression Free Survival (PFS) Time	Time from randomization to PD as determined by the investigator or death. PFS time for subjects without an event will be censored as of the date of last contact.	From first participant randomised up to 5 years	No
Secondary	Time to Treatment Failure	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 have missed two consecutive scheduled doses will be considered as treatment failures and the TTF will be calculated from the date of randomization to the date of their first missed treatment.	From first participant randomized up to 5 years	No
Secondary	Number of subjects with treatment emergent adverse events (TEAEs), serious TEAEs, TEAEs leading to discontinuation and TEAEs leading to death		From the first trial treatment until 42 days after the last trial treatment	Yes