A Study to Demonstrate the Benefit of a New Kind of Anti-cancer Treatment [PReferentially Expressed Antigen of MElanoma (PRAME) Immunotherapy] for Patients With Non-Small Cell Lung Cancer (NSCLC), After Removal of Their Tumor

NCT01853878 | Completed Phase 2 Results

• 2 other identifiers: 1163892012-002790-55
• Study Type: interventional
• Target: 137
• Locations: 9 countries
• Sites: 39

Brief Summary

The purpose of this study was to test a potential new kind of anti-cancer treatment, called PRAME immunotherapy in resected patients with lung cancer. Based on scientific and medical relevance, the clinical study was ended on 24 August 2016. The participants were no longer enrolled in the study, the follow ups on subjects were stopped and the collection and analysis of samples for further research purposes was stopped. After the stop to recruitment, the study was unblinded, as per the amended protocol, the study treatment was continued and completed with the subjects of the active treatment group who were willing to continue. Subjects in the placebo group were withdrawn. There was no longer an active follow-up of patients after discontinuation or completion of the treatment. The study ended 30 days after the last dose was administered. As a result, primary and secondary objectives were not assessed as planned. All clinical and safety data collected in the study were analysed descriptively. For each biological sample already collected in the scope of this study and not tested yet, testing was not performed by default, except if a scientific rationale remained relevant despite the premature termination of the study.

Conditions

Lung Cancer, Non-Small Cell

Keywords

Non-Small Cell Lung Cancer; Immunotherapy; Antigen-Specific

Outcome Measures

Primary Outcomes (1)

• Time to Occurrence of Any Recurrence of Disease

  Time to occurrence of any recurrence of disease was expressed in terms of rate: Person-year rate in each group = number of patients reporting at least one recurrence of disease (n)/ sum of follow-up period expressed in years (T\[year)\]) As a consequence of the decision to stop the PRAME-AS15-NSC-002 (ADJ) study, not all data were available for a full analysis. The median follow-up time was 10.3 months in the GSK2302032A group and 5.7 months in the Placebo group. Considering that two Phase III studies with recMAGE-A3 + AS15 failed to demonstrate clinical efficacy of the MAGE-A3 antigen specific cancer immunotherapeutic, GSK decided to stop the development of all recombinant protein based cancer vaccines and to stop recruitment in all the ongoing clinical studies.

  During the entire study (From Week 1 to Week 112)

Secondary Outcomes (9)

• Overall Survival (OS)

  During the entire study (From Week 1 to Week 112)

• Lung-cancer-specific Survival

  During the entire study (From Week 1 to Week 112)

• Disease-free Specific Survival (DFSS)

  During the entire study (From Week 1 to Week 112)

• DFS (Disease-free Survival) at 2, 3, 4 and 5 Years After Randomization

  During the entire follow-up period (From year 2 to Year 5)

• Number of Subjects With Any Unsolicited Adverse Events (AEs)

  Within the 31-day (Days 0-30) post-vaccine administration period

Study Arms (2)

GSK2302032A Group

EXPERIMENTAL

The patients received 13 administrations GSK2302032A product, as per the following schedule: For the first five doses: 1 dose every 3 weeks. For the remaining 8 doses: 1 dose every 12 weeks.

Biological: Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302032A

Placebo group

PLACEBO COMPARATOR

The patients received 13 administrations of a placebo, as per the following schedule: For the first five doses: 1 dose every 3 weeks. For the remaining 8 doses: 1 dose every 12 weeks.

Biological: Placebo

Interventions

Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302032A BIOLOGICAL

Intramuscular administration

GSK2302032A Group

Placebo BIOLOGICAL

Intramuscular administration

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has radically resected NSCLC
• The NSCLC is of pathological stage IA-T1b, IB, II or IIIA NSCLC The surgical technique for resection of the patient's tumor is anatomical, involving at least a segmentectomy The patient's tumor shows expression of PRAME.
• The patient is ≥ 18 years of age at the time of first consent.
• Written informed consent has been obtained from the patient prior to performance of any study-specific procedure.
• The patient is free of disease (no residual tumor, no loco-regional recurrence, no distant metastasis), as confirmed by a post- thoracic surgery contrast-enhanced computed tomography (CT scan) of the chest, upper abdomen and by a contrast-enhanced CT scan or Magnetic Resonance Imaging (MRI) of the brain. Other examinations should be performed as clinically indicated.
• Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2 at the time of randomization
• Adequate bone-marrow reserve, adequate renal, hepatic and adrenal function as assessed by standard laboratory criteria
• If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study product, have a negative pregnancy test and continue such precautions during all study treatment period and for 2 months after last treatment administration.
• Patients who the investigator believes can and will comply with the requirements of this protocol (e.g. return for active follow-up visits).

You may not qualify if:

• The patient is diagnosed with a concomitant malignancy and/or has a history of malignancy within the past five years or has had a malignancy that has been in complete remission for less than 5 years. Patients with effectively treated non - melanoma skin cancers or effectively treated carcinoma in situ of the cervix both of which in remission for less than 5 years will be eligible.
• The patient has received any anti-cancer specific treatment, including radiotherapy, immunotherapy, hormonal therapy, chemotherapy or neo-adjuvant chemotherapy, except for:
• Administration of adjuvant platinum-based doublet chemotherapy for the treatment of the current NSCLC allowed between surgery and randomization.
• Treatment of previous malignancies as allowed by the protocol.
• The patient has been diagnosed with a Potential Immune-Mediated Disease (pIMD). Patients with vitiligo are not excluded from the study.
• The patient has a history of confirmed adrenal dysfunction.
• The patient requires concomitant treatment with any immunosuppressive agent, or with systemic corticosteroids prescribed for chronic treatment (more than 7 consecutive days).
• The patient needs chronic long term oxygen therapy (LTOT). The patient has medically uncontrolled congestive heart failure or hypertension, unstable heart disease or uncontrolled arrhythmia at the time of randomization.
• The patient has an uncontrolled bleeding disorder.
• The patient has undergone splenectomy.
• The patient is known to be Human Immunodeficiency Virus (HIV)-positive.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.
• The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
• The patient has received any investigational or non-registered product within the 30 days preceding randomization, or planned use during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (39)

GSK Investigational Site

Newark, Delaware, 19713, United States

Location

GSK Investigational Site

Springfield, Illinois, 62702, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Paterson, New Jersey, 08759, United States

Location

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Everett, Washington, 98201, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

GSK Investigational Site

Tallinn, 13419, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Créteil, 94010, France

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Marseille, 13915, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81925, Germany

Location

GSK Investigational Site

Immenhausen, Hesse, 34376, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 51109, Germany

Location

GSK Investigational Site

Herne, North Rhine-Westphalia, 44623, Germany

Location

GSK Investigational Site

Moers, North Rhine-Westphalia, 47441, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48153, Germany

Location

GSK Investigational Site

Velbert, North Rhine-Westphalia, 42551, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Berlin, 13125, Germany

Location

GSK Investigational Site

Hyōgo, 673-8558, Japan

Location

GSK Investigational Site

Kanagawa, 232-0024, Japan

Location

GSK Investigational Site

Kanagawa, 241-8515, Japan

Location

GSK Investigational Site

Shizuoka, 411-8777, Japan

Location

GSK Investigational Site

Szczecin, 70-891, Poland

Location

GSK Investigational Site

Zakopane, 34-500, Poland

Location

GSK Investigational Site

Chelyabinsk, 454087, Russia

Location

GSK Investigational Site

Saint Petersburg, 197 089, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

GSK Investigational Site

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

Manchester, M23 9LT, United Kingdom

Location

GSK Investigational Site

Sheffield, S10 2SJ, United Kingdom

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

As of 18 July 2014, the recruitment was stopped and the study was unblinded. For patients randomized to the placebo group, no further protocol visits were to be performed except for the concluding visit and no further doses were to be administered.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: May 15, 2013
• Study Start: June 12, 2013
• Primary Completion: August 24, 2016
• Study Completion: August 24, 2016
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below).
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (8); ES (2); PL (2); DE (10); JP (4); KR (1); GB (5); RU (3); FR (4)