Tecemotide Following Concurrent Chemo-radiotherapy for Non-small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

— START2  

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Trial of Tecemotide Versus Placebo in Subjects With Completed Concurrent Chemo-radiotherapy for Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02049151
• Other study ID #: EMR 63325-021
• Secondary ID: 2013-003760-30
• Status: Terminated
• Phase: Phase 3
• First received: January 27, 2014
• Last updated: October 8, 2015
• Start date: March 2014
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Federal Office for Safety in Health CareAustralia: Human Research Ethics CommitteeBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlDenmark: National Board of HealthFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Paul-Ehrlich-InstitutIreland: Irish Medicines BoardItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, double-blind, placebo-controlled, randomized, Phase 3 trial in subjects with unresectable stage III non-small cell lung cancer (NSCLC) who have demonstrated either stable disease or objective response following primary concurrent chemo-radiotherapy (CRT), comparing overall survival (OS) time in subjects treated with tecemotide versus subjects treated with tecemotide-matching placebo.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent, before any trial-related activities are carried out

• Histologically or cytologically documented unresectable stage III NSCLC, including bronchioalveolar carcinomas. Cancer stage must be confirmed and documented by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) scan

• Prior concurrent CRT which is defined as follows:

• Minimum of 2 cycles of platinum-based chemotherapy

• Radiotherapy with a total tumor dose greater than equal to (>=) 60 Gray and a single fraction dose >= 1.8 Gray

• Overlap of radiotherapy with minimum 2 cycles of platinum-based chemotherapy (one cycle is defined as either 3 or 4 weeks depending on the chemotherapy regimen). A deviation of 2 to 3 days from an exact overlap is acceptable. Purely radiosensitizing doses of chemotherapy are not acceptable (for example [e.g.], daily low dose regimens; weekly carbo-platinum + paclitaxel regimens are allowed).

• Subjects must have completed the primary thoracic CRT at least 4 weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary CRT are eligible.

• Documented stable disease or objective response, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after primary concurrent CRT for unresectable stage III disease, within 4 weeks (28 days) prior to randomization

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• A platelet count, white blood cells (WBC) and hemoglobin value as defined in the protocol

• Male or female, greater than or equal to 18 years of age

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Undergone lung cancer specific therapy (including surgery) other than initial concurrent CRT

• Received chemotherapy during radiotherapy in radiosensitizing doses only (e.g., daily low dose regimens; weekly carbo-platinum + paclitaxel regimens are allowed).

• Metastatic disease

• Malignant pleural effusion at initial diagnosis, during initial CRT, 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

• A recognized immunodeficiency disease including human immunodeficiency virus (HIV) infection and other cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary, congenital or acquired immunodeficiencies

• Splenectomy

• Any preexisting medical condition requiring chronic systemic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed)

• Receipt of immunotherapy (as defined in the protocol) within 4 weeks prior to randomization

• Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks prior to randomization

• Autoimmune disease

• Active or chronic infectious hepatitis

• Infectious process that, in the opinion of the Investigator, could compromise the subject's ability to mount an immune response

• Clinically significant hepatic dysfunction, renal dysfunction and cardiac disease as defined in the protocol

• Pregnant or breast-feeding women

• Known drug abuse/alcohol abuse

• Participation in another interventional clinical trial within the past 28 days (excluding purely observational studies)

• 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

• Other protocol defined exclusion criteria could apply

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

Intervention

Drug:
• Tecemotide
Tecemotide injection will be administered once weekly subcutaneously at a dose of 806 microgram up to Week 8 and from Week 14, every 6 weeks until end-of-trial, or until NSCLC progression.
• Placebo
Matching placebo injection will be administered once weekly subcutaneously up to Week 8 and from Week 14, every 6 weeks until end-of-trial, or until NSCLC progression.
• Cyclophosphamide (CPA)
CPA injection will be administered as a single intravenous infusion at a dose of 300 milligram per square meter (mg/m^2) (to a maximum of 600 mg) 3 days before the first injection of tecemotide.
• Saline (sodium chloride)
Matching placebo (saline) injection will be administered as a single intravenous (0.9 percent [%] sodium chloride) infusion 3 days before the first injection of tecemotide-matching placebo.

Locations

Country	Name	City	State
Germany	Please contact the Merck KGaA Communication Center Located in	Darmstadt
United States	Please Contact U.S. Medical Information Located in	Rockland	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) Time	OS time will be defined as the duration between the date of randomization and the date of death. For participants not known to be deceased at the time of analysis, the time from the date of randomization to the date of last contact, or date lost to follow-up, will be calculated and used as a censored observation in the analysis.	From the date of randomization up to 12- Week follow-up visit after the last dose of study treatment	No
Secondary	Time to Symptom Progression (TTSP)	TTSP will be measured from date of randomization to date of progression, using the lung cancer symptom scale (LCSS), a validated questionnaire consisting of an observer scale and a subject scale used to specifically measure symptom changes relevant to QoL for individuals undergoing treatment for lung cancer. The subject scale will be used as a tool to determine TTSP. It is a 9-item questionnaire used to document subject-reported outcomes for a variety of lung cancer associated symptoms. The average symptomatic burden index (ASBI) will be used to determine differences in the treatment groups. ASBI is the mean of the 6 symptom scores derived from the LCSS questionnaire. Symptom progression will be defined as an increase (worsening) of the ASBI score of 10% of the scale breadth (10 mm on a scale of 0-100 mm) from the baseline score on at least 2 consecutive assessments during the period when assessments are performed every 3 weeks and every 6 weeks.	From the date of randomization up to 12- Week follow-up visit after the last dose of study treatment	No
Secondary	Progression-free Survival (PFS)	PFS is defined as the time from randomization to the first documentation of progressive disease (PD) or to death due to any cause, whichever occurs first. PD is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Investigator read. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression. For subjects alive without tumor progression at time of analysis, the time between date of randomization and the last date that imaging was performed will be used to calculate PFS time and used as a censored observation in the analysis.	From the date of randomization up to 12- Week follow-up visit after the last dose of study treatment	No
Secondary	Time to Progression (TTP)	TTP will be measured from the date of randomization to the date of tumor progression. The date of tumor progression will be the date of radiological diagnosis of PD, performed as per RECIST 1.1. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression. For participants alive without tumor progression at time of analysis, the time between date of randomization and date of last trial treatment will be calculated and used as a censored observation in the analysis. Participants dying from causes other than PD will be censored at time of death.	From the date of randomization up to 12- Week follow-up visit after the last dose of study treatment	No