A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma

NCT00942162 | Completed Phase 2 Results

• 2 other identifiers: 1114762008-004007-64
• Study Type: interventional
• Target: 125
• Locations: 8 countries
• Sites: 63

Brief Summary

The objective of this study is to evaluate the clinical activity of the GSK2132231A immunotherapeutic in patients with MAGE-A3 positive unresectable metastatic melanoma presenting with the predictive gene signature.

Conditions

Melanoma

Keywords

ASCI; Melanoma; Immunotherapeutic; Tumor antigen; PREDICT

Outcome Measures

Primary Outcomes (2)

• One-year Overall Survival Rate (OSR) Estimated by Complete Case Method

  The 1-year overall survival rate (OSR) in the GS+ Population would be above 50% (target = 71%), a percentage which was reported together with its 95% confidence interval (CI). Maximum 1-year OSR of any currently available treatment in the MAGE-A3-positive population = 50% (P0). This median OS of 12 months is based on the observed median OS for MAGE-A3-positive patients, whose tumor did not present the predictive GS. The target 1-year OSR for patients presenting the predictive GS = 71% (P1). This corresponds to a median OS of 24 months when assuming an exponential distribution of OS.

  Month 0 - Month 12

• Number of Patients Reported With Serious Adverse Events (SAEs)

  Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.

  Month 0 - Month 49

Secondary Outcomes (27)

• Number of Patients With Diseases Characteristics by GS

  Month 0 - Month 49

• Progression-free Survival (PFS) by GS

  Month 0 - Month 24

• Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature

  Month 6, Month 12, Month 24

• Overall Survival (OS) by GS

  Up to 5 years from the time of registration.

• Time to Treatment Failure (TTF) by GS

  Month 0 - Month 24

Study Arms (3)

GSK2132231A GS+ Group

EXPERIMENTAL

Patients with the pre-specified gene signature (GS), who received intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

Biological: Immunotherapeutic GSK2132231A

GSK2132231A GS- Group

EXPERIMENTAL

Patients without the pre-specified gene signature (GS), planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

Biological: Immunotherapeutic GSK2132231A

GSK2132231A GS-unknown Group

EXPERIMENTAL

Patients with unknown gene signature (GS), planned to receive intramuscularly up to 24 doses of MAGE\_A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

Biological: Immunotherapeutic GSK2132231A

Interventions

Immunotherapeutic GSK2132231A BIOLOGICAL

Intramuscular administration

Also known as: MAGE-A3 ASCI

GSK2132231A GS+ Group; GSK2132231A GS- Group; GSK2132231A GS-unknown Group

Eligibility Criteria

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

You may qualify if:

• Male or female patients with histologically proven metastatic cutaneous melanoma that is measurable.
• Patients with regional or distant cutaneous, subcutaneous or lymph-node metastasis can be included in the study, provided the disease is not amenable to curative treatment with surgery. In terms of the AJCC 2002 classification, this includes patients with unresectable stage III melanoma including in-transit metastases or patient with stage IV M1a melanoma.
• Written informed consent obtained from the patient prior to performance of any study specific procedure.
• Patient is \>= 18 years at the time of signature of the informed consent form.
• The patient's tumor shows expression of MAGE-A3, as determined by RT-PCR analysis on a fresh tumor tissue sample obtained during the screening phase.
• Fresh tissue from the same lesion as used for MAGE-A3 expression testing must be available for the testing of the predictive gene signature.
• Formalin-fixed paraffin-embedded (FFPE) tissue must be available for complementary MAGE-A3 and gene signature testing.
• Patient fully recovered from any previous intervention (i.e., biopsy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria
• If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to registration in the trial, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series.
• In the opinion of the investigator, the patient can and will comply with the protocol requirements.

You may not qualify if:

• Patients with unresectable stage IV M1b,c melanoma and patients with ocular and mucosal melanoma.
• The patient has at any time received any systemic anticancer treatment.
• Prior systemic treatment with an immunomodulator or loco-regional radiotherapy is permitted as prior adjuvant treatment provided that the last dose was administered at least 30 days before the registration into this trial;
• Previous adjuvant treatment with a cancer vaccine containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least 8 weeks before registration into the trial.
• Prior isolated limb perfusion is permitted provided that the last dose was administered at least 30 days before registration into this trial
• The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, other immunotherapy, chemotherapy and immunomodulating agents.
• The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids, or any other immunosuppressive agents.
• The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV).
• History of allergic disease or reactions likely to be exacerbated by any component of the ASCI treatment.
• The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancer or carcinoma in situ of the cervix and effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
• The patient has psychiatric or addictive disorders
• The patient has an uncontrolled bleeding disorder.
• The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (63)

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Stuart, Florida, 34994, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48019, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Morristown, New Jersey, 07962-1956, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

GSK Investigational Site

Besançon, 25030, France

Location

GSK Investigational Site

Boulogne, 92104, France

Location

GSK Investigational Site

Brest, 29609, France

Location

GSK Investigational Site

Dijon, 21079, France

Location

GSK Investigational Site

Grenoble, 38043, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75006, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Rouen, 76031, France

Location

GSK Investigational Site

Tours, 37044, France

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Nuremberg, Bavaria, 90419, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97080, Germany

Location

GSK Investigational Site

Marburg, Hesse, 35033, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65191, Germany

Location

GSK Investigational Site

Buxtehude, Lower Saxony, 21614, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany

Location

GSK Investigational Site

Homburg, Saarland, 66421, Germany

Location

GSK Investigational Site

Quedlinburg, Saxony-Anhalt, 06484, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23538, Germany

Location

GSK Investigational Site

Erfurt, Thuringia, 99089, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07740, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Cork, Ireland

Location

GSK Investigational Site

Dublin, 7, Ireland

Location

GSK Investigational Site

Dublin, 9, Ireland

Location

GSK Investigational Site

Galway, Co Galway, Ireland

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Siena, Tuscany, 53100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Krakow, 31-108, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Poznan, 61-866, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Madrid, 28033, Spain

Location

Related Publications (1)

• Saiag P, Gutzmer R, Ascierto PA, Maio M, Grob JJ, Murawa P, Dreno B, Ross M, Weber J, Hauschild A, Rutkowski P, Testori A, Levchenko E, Enk A, Misery L, Vanden Abeele C, Vojtek I, Peeters O, Brichard VG, Therasse P. Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT). Ann Oncol. 2016 Oct;27(10):1947-53. doi: 10.1093/annonc/mdw291. Epub 2016 Aug 8.

  PMID: 27502712 BACKGROUND

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

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 20, 2009
• Study Start: August 14, 2009
• Primary Completion: June 27, 2012
• Study Completion: April 1, 2015
• Last Updated: December 8, 2020
• Results First Posted: September 7, 2018

Record last verified: 2020-12

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 (15); IE (4); DE (20); FR (12); ES (2); RU (2); PL (4); IT (4)