Clinical trial NCT01853878: 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
Official title: GSK2302032A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer, Non-Small Cell
Keywords: Non-Small Cell Lung Cancer
Immunotherapy
Antigen-Specific
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-05-15
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 Subjects in the placebo group were withdrawn.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.

Detailed description: During the treatment period, safety monitoring continued as initially foreseen. Reporting of post-study adverse events (AEs) and serious AEs (SAEs) continued as per protocol. In the best interest of the patient, no more biological samples for protocol research purposes (i.e. serum sampling for humoral immunity, whole blood sampling for pharmacogenetics) were taken.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.
* For female patients: the patient is pregnant or lactating or is planning to become pregnant.

Primary outcomes:
measure: Time to Occurrence of Any Recurrence of Disease
timeFrame: During the entire study (From Week 1 to Week 112)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: During the entire study (From Week 1 to Week 112)
measure: Lung-cancer-specific Survival
timeFrame: During the entire study (From Week 1 to Week 112)
measure: Disease-free Specific Survival (DFSS)
timeFrame: During the entire study (From Week 1 to Week 112)
measure: DFS (Disease-free Survival) at 2, 3, 4 and 5 Years After Randomization
timeFrame: During the entire follow-up period (From year 2 to Year 5)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 31-day (Days 0-30) post-vaccine administration period
measure: Anti-PRAME Antibody Concentrations
timeFrame: At each defined time point from Week 0 till Concluding Visit (Week 112)
measure: Number of Subjects With Any Abnormal Hematological and Biochemical Parameters
timeFrame: During the entire study period (From Week 1 to Week 112)
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: During the entire study (From Week 1 to Week 112)
measure: Number of Subjects With Any Adverse Events (AEs) by Intensity Grade.
timeFrame: From Week 0 to Week 112
Other outcomes:
Locations:
city: Newark
country: United States
facility: GSK Investigational Site
state: Delaware
city: Springfield
country: United States
facility: GSK Investigational Site
state: Illinois
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Manchester
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Everett
country: United States
facility: GSK Investigational Site
state: Washington
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Créteil cedex
country: France
facility: GSK Investigational Site
city: Lyon cedex 08
country: France
facility: GSK Investigational Site
city: Marseille cedex 20
country: France
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Immenhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Herne
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Moers
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Velbert
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Zakopane
country: Poland
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
state: Cambridgeshire
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
state: Midlothian
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: