Phase 2b Randomized Controlled Study of Tecemotide (L-BLP25) for Immunotherapy of NSCLC (Non-Small Cell Lung Cancer)

A Multicenter Phase IIb Randomised, Controlled Study of BLP25 Liposome Vaccine for Active Specific Immunotherapy of Non-Small Cell Lung Cancer

This is a prospective open label, controlled, randomized study to test the safety and efficacy of active specific immunotherapy with tecemotide (L-BLP25) for the treatment of subjects with Stage IIIB or Stage IV non-small cell lung cancer (NSCLC). To be eligible, subjects entering the trial will have to demonstrate either stable disease or a clinical response after first-line treatment (chemotherapy alone, or chemotherapy and radiotherapy) and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Following a 3 week washout period, subjects will be stratified by disease status (either Stage IIIB locoregional disease or Stage IIIB with malignant pleural effusion and Stage IV), and randomized to either best supportive care (BSC) plus tecemotide (L-BLP25) treatment or BSC alone.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
• Intervention / Treatment: Biological: Tecemotide (L-BLP25); Drug: Single low dose cyclophosphamide; Other: Best Supportive Care (BSC)

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Darmstadt, Germany
    • Please contact the Merck KGaA Communication Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage IIIB or Stage IV NSCLC
• Stable disease or a clinical response following first-line treatment, consisting of either chemotherapy alone or chemotherapy and radiotherapy. Subjects must have completed the first-line treatment at least 3 weeks prior to study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (>=) 2
• Ability to understand and willingness to sign a written informed consent
• Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

• Received immunotherapy within 4 weeks prior to study entry
• Received immunosuppressive drugs within 3 weeks prior to study entry
• Subjects with known brain metastases
• 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 or immunodeficiency
• Clinically significant hepatic, renal or cardiac dysfunction
• Subjects with clinically significant active infection
• Pregnant or breast feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator
• Other protocol-defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tecemotide (L-BLP25) plus Best Supportive Care (BSC)	Biological: Tecemotide (L-BLP25); After receiving single low dose cyclophosphamide, subjects will receive 8 consecutive weekly subcutaneous vaccinations with 1000 microgram (mcg) of tecemotide (L-BLP25) at weeks 0, 1, 2, 3, 4, 5, 6 and 7 followed by maintenance vaccinations (1000 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until discontinuation from the study due to ECOG status of 4, participation in alternate trial, serious adverse event, or reasons that preclude assessment of clinical status in the opinion of the investigator, and in case of unavailability of study vaccine.; Drug: Single low dose cyclophosphamide; A single intravenous 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 vaccine treatment.; Other: Best Supportive Care (BSC); The BSC will be provided at the investigator's discretion, and may include palliative radiation, psychosocial support, analgesics and nutritional support. Second-line chemotherapy is permitted when indicated for treatment of progressive disease.
Active Comparator: Best Supportive Care (BSC) Alone	Other: Best Supportive Care (BSC); The BSC will be provided at the investigator's discretion, and may include palliative radiation, psychosocial support, analgesics and nutritional support. Second-line chemotherapy is permitted when indicated for treatment of progressive disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs With Cancer and Leukemia Group B (CALGB) Toxicity Grade 3 or 4	An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious AE was an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with TEAEs, serious TEAEs, TEAEs leading to death, and TEAEs with CALGB toxicity Grade 3 or 4 were reported.	From the first dose of study drug administration until 30 days after the last dose of study drug administration or assessed until cut-off date (15 March 2006)
Overall Survival Time	Time from randomization to death or last day known to be alive. Participants without event were censored at the last date known to be alive or at the clinical cut-off date (15 March 2006), whichever was earlier.	Time from randomization to death or last day known to be alive, reported between day of first participant randomized that is, 08 August 2000, up to cut-off (15 March 2006)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Assessment of Cancer Therapy (FACT-L) Questionnaire Score	Functional Assessment of Cancer Therapy - Lung cancer (FACT-L) is a valid instrument used to measure quality of life (QoL) in participants with cancer consisting of the 27-item FACT-General (G) and 9-item lung cancer subscale (LCS). FACT-G is organized into subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT-L total score=4 subscales + LCS and ranges from 0 to 144. Higher scores indicate better QOL.	At baseline, Week 4, Week 8 and then at 12 Week intervals beginning at week 19 until withdrawal/discontinuation from the study.
Number of Participants With Positive T-cell Proliferation	T-cell proliferation assays were performed and the number of participants with positive mucinous glycoprotein 1 (MUC1) specific T-cell proliferative response were reported.	Time from randomization until cut-off date (15 March 2006)
Number of Participants With Elevated CA27-29 Antigen Levels	CA 27-29 is a blood test used to monitor certain types of cancer. CA 27-29 is the name of an antigen, which is a substance that stimulates your body's defense system. CA27-29 antigen levels were determined on all participants and assessed the disease burden of participants at study entry, evaluated early recurrence, presence of residual disease, continued remission or poor prognosis.	Study entry, Week 8

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Butts C, Murray N, Maksymiuk A, Goss G, Marshall E, Soulieres D, Cormier Y, Ellis P, Price A, Sawhney R, Davis M, Mansi J, Smith C, Vergidis D, Ellis P, MacNeil M, Palmer M. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol. 2005 Sep 20;23(27):6674-81. doi: 10.1200/JCO.2005.13.011.
• Butts C, Maksymiuk A, Goss G, Soulieres D, Marshall E, Cormier Y, Ellis PM, Price A, Sawhney R, Beier F, Falk M, Murray N. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol. 2011 Sep;137(9):1337-42. doi: 10.1007/s00432-011-1003-3. Epub 2011 Jul 9.
• Butts C, Maksymiuk A, Goss G, et al. A multi-centre phase IIB randomized controlled study of BLP25 liposome vaccine (L-BLP25 or Stimuvax) for active specific immunotherapy of non-small cell lung cancer (NSCLC): updated survival analysis. J Thoracic Oncol. 2007 Aug; 2(8), Suppl 4, S332-3.
• Butts C, Anderson H, Maksymiuk A, et al. Long-term safety of BLP25 liposome vaccine (L-BLP25) in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC). J Clin Onc 2009; 27(15S): abstract 3055.

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: October 19, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: B25-LG-304 / EMR 63325-005