Clinical trial NCT00942162: A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma
Official title: GSK2132231A Antigen-Specific Cancer Immunotherapeutic as First-line Treatment of Patients With Unresectable Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: ASCI
Melanoma
Immunotherapeutic
Tumor antigen
PREDICT
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-07-20
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.

As of Amendment 2, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end approximately 30 days after the last dose will be administered.

In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.

Blood sampling for safety monitoring as per protocol will continue.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Use of any investigational or non-registered product (drug or vaccine) other than the study medication within the 30 days preceding the first investigational treatment injection or planned use during the study period.
* Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). For female patients: the patient is pregnant or lactating.

Primary outcomes:
measure: One-year Overall Survival Rate (OSR) Estimated by Complete Case Method
timeFrame: Month 0 - Month 12
measure: Number of Patients Reported With Serious Adverse Events (SAEs)
timeFrame: Month 0 - Month 49
Secondary outcomes:
measure: Number of Patients With Diseases Characteristics by GS
timeFrame: Month 0 - Month 49
measure: Progression-free Survival (PFS) by GS
timeFrame: Month 0 - Month 24
measure: Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature
timeFrame: Month 6, Month 12, Month 24
measure: Overall Survival (OS) by GS
timeFrame: Up to 5 years from the time of registration.
measure: Time to Treatment Failure (TTF) by GS
timeFrame: Month 0 - Month 24
measure: Best Overall Response (BOR) by GS
timeFrame: Month 0 - Month 24
measure: Duration of Response (CR or PR)
timeFrame: Month 0 - Month 24
measure: Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS
timeFrame: Month 0 - Month 24
measure: Number of Seropositive Patients for Anti-MAGE-A3
timeFrame: PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49).
measure: Anti-MAGE-A3 Antibody Concentrations
timeFrame: PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)
measure: Number of Seropositive Patients for Protein D
timeFrame: PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)
measure: Concentrations of Antibodies Against Protein D (Anti-PD)
timeFrame: PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)
measure: Anti-MAGE-A3 Antibody Response
timeFrame: PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)
measure: Anti-PD Antibody Response
timeFrame: PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)
measure: Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade
timeFrame: Month 0 - Month 49 (each patient was censored out of the analysis at time of death)
measure: Number of Patients With Autoimmune Diseases or Immune-mediated Inflammatory Disorders
timeFrame: Month 0 - Month 49
measure: Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.
timeFrame: Through 30 days after the last administration of the study treatment, approximately 49 months
measure: Number of Patients Reported With Unsolicited AE(s)
timeFrame: Through 30 days after the last administration of the study treatment, approximately 49 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Stuart
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Morristown
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Besançon cedex
country: France
facility: GSK Investigational Site
city: Boulogne
country: France
facility: GSK Investigational Site
city: Brest
country: France
facility: GSK Investigational Site
city: Dijon
country: France
facility: GSK Investigational Site
city: Grenoble
country: France
facility: GSK Investigational Site
city: Marseille Cedex 5
country: France
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Rouen
country: France
facility: GSK Investigational Site
city: Tours
country: France
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Nuernberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Marburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Buxtehude
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Ludwigshafen
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Homburg
country: Germany
facility: GSK Investigational Site
state: Saarland
city: Quedlinburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Erfurt
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Cork
country: Ireland
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Galway
country: Ireland
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Siena
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Kraków
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.