Clinical trial NCT00455572: Cancer Immunotherapy GSK1572932A as Adjuvant Therapy for Patients With Tumor-antigen-positive Non-Small Cell Lung Cancer
Official title: Cancer Immunotherapeutic GSK1572932A as Adjuvant Therapy for Patients With MAGE-A3-positive Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lung Cancer, Non-Small Cell
Keywords: Immunotherapeutic
Adjuvant cancer therapy
Non-small-cell lung cancer
ASCI
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-03
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The anti-MAGE-A3 seroconversion
timeFrame: After the fourth dose of ASCI and at the end of treatment
measure: The anti-protein D seroconversion
timeFrame: After the fourth dose of ASCI and at the end of treatment
measure: The anti-CpG seroconversion
timeFrame: After the fourth dose of ASCI and at the end of treatment
measure: The MAGE-A3 cellular (T cell) response
timeFrame: After the fourth dose of ASCI and at the end of treatment
measure: Occurrence of adverse events, including abnormal hematological and biochemical laboratory values
timeFrame: During the study
measure: Occurrence of serious adverse events
timeFrame: During the study
Secondary outcomes:
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montpellier
country: France
facility: GSK Investigational Site
city: Pierre Benite
country: France
facility: GSK Investigational Site
city: Saint Herblain
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Hemer
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Bad Berka
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Udine
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Wythenshawe
country: United Kingdom
facility: GSK Investigational Site
state: Greater Manchester
city: Bebington, Wirral
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.