Clinical trial NCT01213472: Evaluation of a New Anti-cancer Immunotherapy in Patients With Non-operable and Progressing Metastatic Cutaneous Melanoma
Official title: Study of GSK2241658A Antigen-Specific Cancer Immunotherapeutic in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: ASCI
melanoma
tumor antigen
unresectable
progressive
NY-ESO-1
adult
cancer-testis antigen
Immunotherapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-10-04
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety, immunogenicity and clinical activity of GSK2241658A antigen-specific cancer immunotherapeutic (ASCI) for the treatment of patients with non-operable and progressing metastatic cutaneous melanoma.

Detailed description: In this study, patients were to receive a maximum of 24 doses of recNY-ESO-1 + AS15 ASCI 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 3, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end 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 patient with histologically proven, measurable metastatic cutaneous melanoma, and with documented progressive disease within the 12 weeks before the first administration of study treatment.
* Written informed consent for NY-ESO-1 expression screening and gene profiling on resected tumor tissue and for the complete study has been obtained from the patient prior to shipment of the sample for expression testing and prior to the performance of any other protocol-specific procedure.
* Patient is \>= 18 years of age at the time of signature of the informed consent.
* The patient's tumor shows expression of NY-ESO-1, as determined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis or any updated technique on fresh tissue sample(s).
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* The patient has normal organ functions as shown by all of the following:

  * Hemoglobin ≥ 12 g/dL
  * Absolute leukocytes count ≥ 3.0 x 1000000000/L
  * Absolute lymphocytes count ≥ 1.0 x 1000000000/L
  * Platelets ≥ 100 x 1000000000/L
  * Serum creatinine ≤ Upper Limit of Normal (ULN)
  * Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's syndrome for whom the limit is 2 x ULN)
  * Lactate dehydrogenase ≤ ULN
  * Aspartate aminotransferase ≤ 2 × ULN
  * Alanine aminotransferase ≤ 2 × ULN

These tests must be done no more than 3 weeks before the first ASCI administration.

* Female patients of non-childbearing potential may be enrolled in the study.
* Female patient of childbearing potential may be enrolled in the study, if the patient:

  * has practiced adequate contraception for 30 days prior to first ASCI administration, and
  * has a negative pregnancy test at the specified study visits, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the ASCI administration series.
* In the view of the investigator, the patient can and will comply with the requirements of this protocol.

Exclusion Criteria:

* The patient has at any time received systemic chemotherapy, biochemotherapy, small molecules or nti-CTLA-4 monoclonal antibody for metastatic disease.
* The patient is scheduled to receive any other anticancer treatments than those specified in the protocol, including but not limited to (bio-) chemotherapeutic, immunomodulating agents and radiotherapy.
* The patient received any cancer immunotherapy containing a NY-ESO-1 antigen or any cancer immunotherapy for his/her metastatic disease.
* The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
* Use of any investigational or non-registered product other than the ASCI within 30 days preceding the first ASCI administration, or planned use during the study period.
* The patient has (had) previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
* The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
* The patient has an 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 the Human Immunodeficiency Virus.
* The patient has an uncontrolled bleeding disorder.
* The patient has a family history of congenital or hereditary immunodeficiency.
* 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 concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
* For female patients: the patient is pregnant or lactating.

Primary outcomes:
measure: Number of Patients With Severe Toxicities During the Study Treatment Period
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Number of Patients With Severe Toxicities During the Follow-up Period
timeFrame: During the one year follow-up period (i.e. from Month 49 until Month 61)
measure: Number of Patients With the Best Overall Response in the Overall Population
timeFrame: During the study treatment period (maximum duration = 49 months).
Secondary outcomes:
measure: Number of Patients With Best Overall Response Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Number of Patients With Objective Clinical Response (CR or PR) in the Population of Patients Who Present the Predictive Melanoma Antigen A3 (MAGE-A3) Gene Signature
timeFrame: After 12, 22, 31 and 54 weeks of treatment.
measure: Number of Patients With Adverse Events (AEs) by Maximum Grade
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Number of Patients With Adverse Events (AEs) That Are Causally Related to Treatment Administration by Maximum Grade
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Number of Patients With Serious Adverse Events (SAEs) by Maximum Grade
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Number of Patients With Serious Adverse Events (SAEs) That Are Causally Related to Treatment Administration by Maximum Grade
timeFrame: During the study treatment period (maximum duration = 49 months).
measure: Time to Treatment Failure (TTF)
timeFrame: From first treatment administration (i.e. at Week 0) until the last treatment administration (i.e. at Month 48)
measure: Progression-free Survival (PFS) Rate
timeFrame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)
measure: Overall Survival (OS)
timeFrame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)
measure: The Duration of Response for Patients With CR, PR or Stable Disease (SD) Status
timeFrame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)
measure: Number of Patients With Progression-free Survival Events
timeFrame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)
measure: Summary of Deaths Related to Progressive Disease of Cancer Under Study Reported After the Study Treatment, in the Period of Long-term Follow-up for Survival
timeFrame: During the long-term Follow-Up period for progressive disease and survival [1 year after the study treatment end (at Month 49) or up to 5 years after the first study treatment administration, regardless of disease progression and study discontinuation.]
measure: Anti NY-ESO-1 Antibody Concentrations
timeFrame: Before treatment (PRE), at 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST)
measure: Humoral Response for Anti NY-ESO-1 Antibodies
timeFrame: At 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST)
measure: Cell Mediated Immune Response for Anti-NY-ESO-1 Antibodies (T-cell)
timeFrame: Before treatment (PRE), at 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST)
Other outcomes:
Locations:
city: North Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Graz
country: Austria
facility: GSK Investigational Site
city: Marseille Cedex 5
country: France
facility: GSK Investigational Site
city: Montpellier cedex 5
country: France
facility: GSK Investigational Site
city: Nantes Cedex 1
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
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: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Siena
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Genève
country: Switzerland
facility: GSK Investigational Site
city: Zürich
country: Switzerland
facility: GSK Investigational Site
city: Chelmsford
country: United Kingdom
facility: GSK Investigational Site
city: Leicester
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: American Joint Committee on Cancer. 2002. Cancer staging manual. Sixth edition. Springer editions.