Cancer Immunotherapy GSK1572932A as Adjuvant Therapy for Patients With Tumor-antigen-positive Non-Small Cell Lung Cancer

Cancer Immunotherapeutic GSK1572932A as Adjuvant Therapy for Patients With MAGE-A3-positive Non-Small Cell Lung Cancer

The purpose of this clinical trial is to find out how successfully non-small-cell lung cancer patients are able to give an immune response to injections of the immunotherapeutic product GSK1572932A, and to find out more about the safety of this treatment. A course of eight injections will be administered over 21 weeks; including screening for suitability and all tests, the duration of the study for a patient will be 30-35 weeks. During this period various tests will be performed, including physical examinations and blood tests. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer, Non-Small Cell
• Intervention / Treatment: Biological: Immunotherapeutic GSK1572932A; Drug: Cisplatin (CDDP); Drug: Vinorelbine; Procedure: Radiotherapy

Detailed Description

This is an open, four-arm, parallel-group study, to be conducted at approximately 20 centers in Europe and Canada. All patients will receive the same immunotherapeutic treatment with GSK1572932A, but they will be recruited into four cohorts according to the details of their disease. Cohort 1: Patients with resected stage IB, II or IIIA tumors who are due for standard chemotherapy with cisplatin and vinorelbine. These patients will receive chemo-and immunotherapy in parallel. Cohort 2: Patients with resected stage IB, II or IIIA tumors who are due for standard chemotherapy with cisplatin and vinorelbine. These patients will first receive chemotherapy and then immunotherapy.

Cohort 3: Patients with resected stage IB, II or IIIA tumors who are not due for chemotherapy. These patients will receive immunotherapy only. Cohort 4: Patients with unresectable stage III tumors, following standard chemotherapy and/or radiotherapy. These patients will receive immunotherapy only. Immunotherapeutic treatment will comprise eight doses of GSK1572932A. Doses will be administered at three-week intervals; in Cohort 1 this may be adapted to fit in with the patient's chemotherapy. During the study, adjuvant radiotherapy is allowed in Cohorts 1, 2 and 3 for patients in stage III only and is prohibited in Cohort 4. Chemotherapy during the study is allowed in Cohort 1 only as described above, and is prohibited in Cohorts 2-4. The total maximum duration of the study for a patient will be 30-35 weeks.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • GSK Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H4J 1C5
      • GSK Investigational Site
• France
  • Montpellier, France, 34295
    • GSK Investigational Site
  • Pierre Benite, France, 69495
    • GSK Investigational Site
  • Saint Herblain, France, 44805
    • GSK Investigational Site
  • Strasbourg, France, 67091
    • GSK Investigational Site
• Germany
  • Hamburg, Germany, 20246
    • GSK Investigational Site
  • Nordrhein-Westfalen
    • Hemer, Nordrhein-Westfalen, Germany, 58675
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
      • GSK Investigational Site
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22927
      • GSK Investigational Site
  • Thueringen
    • Bad Berka, Thueringen, Germany, 99437
      • GSK Investigational Site
• Italy
  • Friuli-Venezia-Giulia
    • Udine, Friuli-Venezia-Giulia, Italy, 33100
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00152
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20141
      • GSK Investigational Site
• United Kingdom
  • Bebington, Wirral, United Kingdom, CH63 4JY
    • GSK Investigational Site
  • London, United Kingdom, SE1 9RT
    • GSK Investigational Site
  • Nottingham, United Kingdom, NG5 1PB
    • GSK Investigational Site
  • Southampton, United Kingdom, SO16 6YD
    • GSK Investigational Site
  • Greater Manchester
    • Wythenshawe, Greater Manchester, United Kingdom, M23 9LT
      • GSK Investigational Site

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:

• Written informed consent obtained,
• Aged 18 or more,
• Pathologically proven stage IB, II or III NSCLC,
• Tumor expresses MAGE-A3,
• Free of distant metastasis,

• For Cohort 1, all of the following:

  1. Completely resected stage IB, II or IIIA NSCLC,
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG performance status = 0 or 1
  4. Due to receive adjuvant chemotherapy as permitted in the protocol
  5. Not received, not receiving, and not due to receive adjuvant radiotherapy (except stage III patients)
  6. First administration of chemotherapy can be scheduled within 4-12 weeks after surgery

• For Cohort 2, all of the following:

  1. Resected stage IB, II or IIIA NSCLC,
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG PS = 0 or 1
  4. Due to receive, or receiving, adjuvant chemotherapy as permitted in the protocol
  5. Not received, not receiving, and not due to receive, adjuvant radiotherapy (except stage III patients)
  6. First administration of ASCI treatment can be scheduled within 2-4 weeks after the last administration of chemotherapy
  7. Received at least 2 cycles of standard chemotherapy before ASCI treatment is initiated, whereafter no further chemotherapy is planned

• For Cohort 3, all of the following:

  1. Resected stage IB, II or IIIA NSCLC
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG PS = 0 or 1 or 2
  4. Not received, not receiving, and not due to receive, adjuvant chemotherapy
  5. Not received, not receiving, and not due to receive, adjuvant radiotherapy (this does not apply to patients in stage III)
  6. First administration of ASCI treatment can be scheduled within 4-8 weeks after surgery

• For Cohort 4, all of the following:

  1. Unresectable stage III NSCLC
  2. ECOG PS = 0 or 1 or 2
  3. Due to receive, or receiving, chemo- and radiotherapy according to institution standard
  4. Received at least 2 cycles of standard chemotherapy before the initiation of ASCI treatment, whereafter no further chemo-/radiotherapy is planned
  5. Stable disease or objective response (confirmed by CT scan) after standard chemo-/radiotherapy
  6. Administration of ASCI treatment can be scheduled within 2-6 weeks after the last administration of chemo-/radiotherapy
• Laboratory criteria: adequate bone-marrow reserve, adequate renal function, adequate hepatic function.
• For females: EITHER not of child-bearing potential, OR sexually abstinent, OR negative urine pregnancy test + use of adequate contraceptive precautions from 30 days before first study treatment till 2 months after completion of study treatment course
• In the view of the investigator, the patient can and will comply with the requirements of the protocol

Exclusion criteria:

• Previous or concomitant other malignancies, except if effectively treated and considered by the investigator highly likely to have been cured
• Pregnant or lactating
• History of anaphylaxis or severe allergic reaction
• Concurrent severe medical problems, unrelated to the malignancy, limiting full compliance with the study or exposing the patient to unacceptable risk
• Psychiatric or addictive disorders compromising the ability to give informed consent, or to comply with the trial procedures
• HIV-positive
• Require treatment with systemic corticosteroids, or other immunosuppressive agents
• Need home oxygenation
• Received or plan to receive investigational or non-registered product other than the study medication from 30 days before first dose of study medication and during whole study period
• History of chronic alcohol consumption and/or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Patients with resected stage IB, II or IIIA tumors who are due for standard chemotherapy with cisplatin and vinorelbine. These patients will receive chemo-and immunotherapy in parallel.	Biological: Immunotherapeutic GSK1572932A; Intramuscular injection, 8 doses; Drug: Cisplatin (CDDP); Four cycles with doses based on patient's body surface area, intravenous administration; Drug: Vinorelbine; Four cycles with doses based on patient's body surface area , intravenous administration
EXPERIMENTAL: Cohort 2; Patients with resected stage IB, II or IIIA tumors who are due for standard chemotherapy with cisplatin and vinorelbine. These patients will first receive chemotherapy and then immunotherapy	Biological: Immunotherapeutic GSK1572932A; Intramuscular injection, 8 doses; Drug: Cisplatin (CDDP); Four cycles with doses based on patient's body surface area, intravenous administration; Drug: Vinorelbine; Four cycles with doses based on patient's body surface area , intravenous administration
EXPERIMENTAL: Cohort 3; Patients with resected stage IB, II or IIIA tumors who are not due for chemotherapy. These patients will receive immunotherapy only.	Biological: Immunotherapeutic GSK1572932A; Intramuscular injection, 8 doses
EXPERIMENTAL: Cohort 4; Patients with unresectable stage III tumors, following standard chemotherapy and/or radiotherapy. These patients will receive immunotherapy only.	Biological: Immunotherapeutic GSK1572932A; Intramuscular injection, 8 doses; Drug: Cisplatin (CDDP); Four cycles with doses based on patient's body surface area, intravenous administration; Drug: Vinorelbine; Four cycles with doses based on patient's body surface area , intravenous administration; Procedure: Radiotherapy; Regimen will be based upon the site's own standard procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The anti-MAGE-A3 seroconversion	After the fourth dose of ASCI and at the end of treatment
The anti-protein D seroconversion	After the fourth dose of ASCI and at the end of treatment
The anti-CpG seroconversion	After the fourth dose of ASCI and at the end of treatment
The MAGE-A3 cellular (T cell) response	After the fourth dose of ASCI and at the end of treatment
Occurrence of adverse events, including abnormal hematological and biochemical laboratory values	During the study
Occurrence of serious adverse events	During the study

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Pujol JL, Vansteenkiste JF, De Pas TM, Atanackovic D, Reck M, Thomeer M, Douillard JY, Fasola G, Potter V, Taylor P, Bosquee L, Scheubel R, Jarnjak S, Debois M, de Sousa Alves P, Louahed J, Brichard VG, Lehmann FF. Safety and Immunogenicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive Non-Small-Cell Lung Cancer. J Thorac Oncol. 2015 Oct;10(10):1458-67. doi: 10.1097/JTO.0000000000000653.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 11, 2007
• Primary Completion (ACTUAL): August 4, 2013
• Study Completion (ACTUAL): August 8, 2013

Study Registration Dates

• First Submitted: April 2, 2007
• First Submitted That Met QC Criteria: April 2, 2007
• First Posted (ESTIMATE): April 3, 2007

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 12, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Non-small-cell lung cancer; Immunotherapeutic; ASCI; Adjuvant cancer therapy
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Cisplatin; Vinorelbine
• Other Study ID Numbers: 107240

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 107240
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register