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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 (PEARL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853878
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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 Subjects in the placebo group were withdrawn.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.


Condition or disease Intervention/treatment Phase
Lung Cancer, Non-Small Cell Biological: Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302032A Biological: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 137 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: GSK2302032A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer
Actual Study Start Date : June 12, 2013
Actual Primary Completion Date : August 24, 2016
Actual Study Completion Date : August 24, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GSK2302032A Group
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
Intramuscular administration

Placebo Comparator: Placebo group
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
Intramuscular administration




Primary Outcome Measures :
  1. Time to Occurrence of Any Recurrence of Disease [ Time Frame: During the entire study (From Week 1 to Week 112) ]
    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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: During the entire study (From Week 1 to Week 112) ]
    OS was defined as the interval from randomization to the date of death, irrespective of the cause of death; patients still alive were censored at the last visit they are known to be alive. 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. Therefore, based on scientific and medical relevance, the decision was made to stop patient enrollment in the PRAME-AS15-NSC-002 (ADJ) clinical study and to stop follow-up visits, further sample collection for research purposes and the analysis of samples for research purposes. In consequence, the primary and secondary outcomes were not analysed as planned and clinical data for this outcome was not collected.

  2. Lung-cancer-specific Survival [ Time Frame: During the entire study (From Week 1 to Week 112) ]
    Lung-cancer specific survival was defined as defined as the interval from randomization to the date of death due to lung cancer; deaths due to other or unknown causes were censored at the date of death. 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. Therefore, based on scientific and medical relevance, the decision was made to stop patient enrollment in the PRAME-AS15-NSC-002 (ADJ) clinical study and to stop follow-up visits, further sample collection for research purposes and the analysis of samples for research purposes. In consequence, the primary and secondary outcomes were not analysed as planned and clinical data for this outcome was not collected.

  3. Disease-free Specific Survival (DFSS) [ Time Frame: During the entire study (From Week 1 to Week 112) ]
    DFSS was defined as the interval from randomization to the date of first recurrence of disease or date of death due to lung cancer, whichever occurs first. Patients without recurrence or death due to lung cancer were censored at the date of last assessment. 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. Therefore, based on scientific and medical relevance, the decision was made to stop patient enrollment in the PRAME-AS15-NSC-002 (ADJ) clinical study and to stop follow-up visits, further sample collection for research purposes and the analysis of samples for research purposes. In consequence, the primary and secondary outcomes were not analysed as planned and clinical data for this outcome was not collected.

  4. DFS (Disease-free Survival) at 2, 3, 4 and 5 Years After Randomization [ Time Frame: During the entire follow-up period (From year 2 to Year 5) ]
    Defined as the time from randomization to either the date of first recurrence of the disease or the date of death (whatever the cause), whichever occurred first. The 5-year active follow-up period planned in the initial study protocol was cancelled per Protocol Amendment 2, hence this analysis was not performed.

  5. Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: Within the 31-day (Days 0-30) post-vaccine administration period ]
    Unsolicited AEs covered any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  6. Anti-PRAME Antibody Concentrations [ Time Frame: At each defined time point from Week 0 till Concluding Visit (Week 112) ]
    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. Therefore, based on scientific and medical relevance, the decision was made to stop patient enrollment in the PRAME-AS15-NSC-002 (ADJ) clinical study and to stop follow-up visits, further sample collection for research purposes and the analysis of samples for research purposes. In consequence, the primary and secondary outcomes were not analysed as planned and clinical data for this outcome was not collected.

  7. Number of Subjects With Any Abnormal Hematological and Biochemical Parameters [ Time Frame: During the entire study period (From Week 1 to Week 112) ]
    Hematological and biochemical parameters assessed were tabulated by maximum grade versus baseline, by CTCAE = Common Terminology Criteria for Adverse Events version 4.0 (Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening; Grade 5 = death; Grade Unknown) and by the type of abnormality (e.g. increased, decreased, prolonged, etc.). Some parameters (e.g. Anemia) already comprise within their definition the type of abnormality presented.

  8. Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: During the entire study (From Week 1 to Week 112) ]
    SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. An event that was part of the natural course of the disease under study (i.e., disease progression, recurrence) was captured in the study as an efficacy measure; therefore it did not need to be reported as an SAE.

  9. Number of Subjects With Any Adverse Events (AEs) by Intensity Grade. [ Time Frame: From Week 0 to Week 112 ]
    Grading was done as per the Common Terminology Criteria for Adverse Events (CTCAE) of the U.S. National Cancer Institute, version 4.0. The intensity grades assessed were: 1, 2, 3, 4, 5 and Unknown.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01853878


Locations
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United States, Delaware
GSK Investigational Site
Newark, Delaware, United States, 19713
United States, Illinois
GSK Investigational Site
Springfield, Illinois, United States, 62702
United States, Minnesota
GSK Investigational Site
Rochester, Minnesota, United States, 55905
United States, New Jersey
GSK Investigational Site
Manchester, New Jersey, United States, 08759
United States, New York
GSK Investigational Site
New York, New York, United States, 10021
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
GSK Investigational Site
Everett, Washington, United States, 98201
GSK Investigational Site
Seattle, Washington, United States, 98104
Estonia
GSK Investigational Site
Tallinn, Estonia, 13419
GSK Investigational Site
Tartu, Estonia, 51014
France
GSK Investigational Site
Créteil cedex, France, 94010
GSK Investigational Site
Lyon cedex 08, France, 69373
GSK Investigational Site
Marseille cedex 20, France, 13915
GSK Investigational Site
Montpellier, France, 34295
Germany
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69126
GSK Investigational Site
Muenchen, Bayern, Germany, 81925
GSK Investigational Site
Immenhausen, Hessen, Germany, 34376
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44623
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51109
GSK Investigational Site
Moers, Nordrhein-Westfalen, Germany, 47441
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48153
GSK Investigational Site
Velbert, Nordrhein-Westfalen, Germany, 42551
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
GSK Investigational Site
Berlin, Germany, 13125
Japan
GSK Investigational Site
Hyogo, Japan, 673-8558
GSK Investigational Site
Kanagawa, Japan, 232-0024
GSK Investigational Site
Kanagawa, Japan, 241-8515
GSK Investigational Site
Shizuoka, Japan, 411-8777
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
Poland
GSK Investigational Site
Szczecin, Poland, 70-891
GSK Investigational Site
Zakopane, Poland, 34-500
Russian Federation
GSK Investigational Site
Chelyabinsk, Russian Federation, 454087
GSK Investigational Site
St. Petersburg, Russian Federation, 197 089
GSK Investigational Site
St. Petersburg, Russian Federation, 197758
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
GSK Investigational Site
Edinburgh, Midlothian, United Kingdom, EH4 2XU
GSK Investigational Site
Birmingham, United Kingdom, B9 5SS
GSK Investigational Site
Manchester, United Kingdom, M23 9LT
GSK Investigational Site
Sheffield, United Kingdom, S10 2SJ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
Additional Information:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 116389
For additional information about this study please refer to the GSK Clinical Study Register

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01853878    
Other Study ID Numbers: 116389
2012-002790-55 ( EudraCT Number )
First Posted: May 15, 2013    Key Record Dates
Results First Posted: August 28, 2019
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicalstudydatarequest.com
Keywords provided by GlaxoSmithKline:
Non-Small Cell Lung Cancer
Immunotherapy
Antigen-Specific
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms