Clinical trial NCT00849875: A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients
Official title: Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Association With Chemotherapy in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Melanoma
Keywords: ASCI
Dacarbazine
Cancer immunotherapeutic
MAGE-A3
Malignant melanoma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-02-24
Enrollment: 48
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 clinical trial is to find out how successfully, patients with progressive metastatic cutaneous melanoma, are able to develop an immune response to injections with the immunotherapeutic product GSK1572932A when given in combination with dacarbazine and evaluate the safety of this combination.

Detailed description: This Protocol Posting has been updated following amendment 3, dated 16 October 2009. The sections impacted are :

* Enrollment, number of subjects
* Outcome measures
* Exclusion criteria

Eligibility criteria: Inclusion Criteria:

1. Male or female patient with histologically proven, measurable metastatic cutaneous melanoma
2. Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
3. Patient is \>= 18 years of age at the time of signature of the Informed Consent.
4. The patient's tumor shows expression of MAGE-A3 antigen, detected by Reverse-Transcription Polymerase Chain Reaction (RT-PCR).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. The patient has normal organ functions.
7. 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 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during all the study treatment period and for 2 months after completion of the treatment administration series.
8. In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Exclusion Criteria:

1. The patient has at any time received systemic (bio)-chemotherapy.
2. The patient is scheduled to receive any other anticancer treatments than those specified in the protocol, including but not limited to (bio)-chemotherapy, immunomodulating agents and radiotherapy.
3. The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
4. The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen or any cancer immunotherapeutic for his/her metastatic disease.
5. The patient has received any investigational or non-registered drug or vaccine other than the study medication within the 30 days preceding the first dose of study treatment, or plans to receive such a drug during the study period.
6. The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
7. History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
8. 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.
9. The patient has a family history of congenital or hereditary immunodeficiency.
10. The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.
12. 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.
13. For female patients: the patient is pregnant or lactating.
14. The patient has an uncontrolled bleeding disorder.

Primary outcomes:
measure: Number of Patients Reported With Unsolicited Adverse Events (AEs) That Were Causally Related to Treatment Administration by Maximum Grade.
timeFrame: Within the 31-day (Days 0-30) post-administration period.
measure: Number of Patients Reported With Serious Adverse Events (SAEs)
timeFrame: During the entire study period, up to 5 years
measure: Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3)
timeFrame: Post Dose 4 at Week 13 (W13).
measure: Anti-MAGE-A3 Antibody Concentrations
timeFrame: Post Dose 4 at Week 13 (W13).
measure: Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies
timeFrame: Post Dose 4 at Week 13 (W13).
measure: Concentrations of Antibodies Against Protein D (Anti-PD)
timeFrame: Post Dose 4 at Week 13 (W13).
measure: Number of Patients With Treatment Response for Anti-PD
timeFrame: Post Dose 4 at Week 13 (W13).
measure: Anti-MAGE-A3 Antibody Concentrations (CMI)
timeFrame: Post Dose 4 at Week 13 (W13).
Secondary outcomes:
measure: Number of Patients With Objective Tumor Response (OR) to MAGE-A3 ASCI Study Treatment
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Stable Disease (SD) Response to MAGE-A3 ASCI Study Treatment
timeFrame: During the entire study, up to 5 years
measure: Duration of Stable Disease (SD) Response to MAGE-A3 ASCI Study Treatment
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Mixed Response (MxR) to MAGE-A3 ASCI Study Treatment
timeFrame: During the entire study, up to 5 years
measure: Time to Treatment Failure (TTF), by Gene Signature
timeFrame: During the entire study, up to 5 years
measure: Progression-free Survival (PFS) for the Overall Population
timeFrame: During the entire study, up to 5 years
measure: Progression-free Survival (PFS) by Gene Signature
timeFrame: During the entire study, up to 5 years
measure: Progression-free Survival (PFS) After Slow Progressive Disease (SPD) by Gene Signature
timeFrame: During the entire study, up to 5 years
measure: Overall Survival (OS) by Gene Signature
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade.
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Gamma-glutamyl Transpeptidase (GGT) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hypercalcemia (HCA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hyperkalemia (HKA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hypernatremia (HNA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hypoalbuminemia(hAL) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hypocalcemia(hCA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hypokalemia (hKA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Hyponatremia (hNA) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Partial Thromboplastin Time (PTT) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Abnormal Platelets(PLT) Values by Maximum Grade
timeFrame: During the entire study, up to 5 years
measure: Number of Patients With Any Adverse Events (AEs) and With AEs by Maximum Grade
timeFrame: Within the 31-day follow-up period post treatment administration.
measure: Number of Patients With Any Serious Adverse Events (SAEs) and With AEs by Maximum Grade
timeFrame: Within the 31-day follow-up period post treatment administration.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Brussel
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Roeselare
country: Belgium
facility: GSK Investigational Site
city: Yvoir
country: Belgium
facility: GSK Investigational Site
city: Caen
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Marseille Cedex 5
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Reims
country: France
facility: GSK Investigational Site
city: Villejuif
country: France
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Grob JJ, Mortier L, D'Hondt L, Grange F, Baurain JF, Dreno B, Lebbe C, Robert C, Dompmartin A, Neyns B, Gillet M, Louahed J, Jarnjak S, Lehmann FF. Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature. ESMO Open. 2017 Nov 14;2(5):e000203. doi: 10.1136/esmoopen-2017-000203. eCollection 2017.