A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients

NCT00849875 | Terminated Phase 2 Results

• 1 other identifier: 111714
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 14

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.

Conditions

Melanoma

Keywords

ASCI; Dacarbazine; Cancer immunotherapeutic; MAGE-A3; Malignant melanoma

Outcome Measures

Primary Outcomes (8)

• Number of Patients Reported With Unsolicited Adverse Events (AEs) That Were Causally Related to Treatment Administration by Maximum Grade.

  The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the treatment.

  Within the 31-day (Days 0-30) post-administration period.

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

  Serious adverse events (SAEs) assessed include 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.

  During the entire study period, up to 5 years

• Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3)

  Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27.

  Post Dose 4 at Week 13 (W13).

• Anti-MAGE-A3 Antibody Concentrations

  Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL)

  Post Dose 4 at Week 13 (W13).

• Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies

  Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration

  Post Dose 4 at Week 13 (W13).

• Concentrations of Antibodies Against Protein D (Anti-PD)

  Anti-PD antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL).

  Post Dose 4 at Week 13 (W13).

• Number of Patients With Treatment Response for Anti-PD

  Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 100 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration

  Post Dose 4 at Week 13 (W13).

• Anti-MAGE-A3 Antibody Concentrations (CMI)

  Analysis of MAGE-A3 cellular response was not performed and data were not collected..

  Post Dose 4 at Week 13 (W13).

Secondary Outcomes (30)

• Number of Patients With Objective Tumor Response (OR) to MAGE-A3 ASCI Study Treatment

  During the entire study, up to 5 years

• Number of Patients With Stable Disease (SD) Response to MAGE-A3 ASCI Study Treatment

  During the entire study, up to 5 years

• Duration of Stable Disease (SD) Response to MAGE-A3 ASCI Study Treatment

  During the entire study, up to 5 years

• Number of Patients With Mixed Response (MxR) to MAGE-A3 ASCI Study Treatment

  During the entire study, up to 5 years

• Time to Treatment Failure (TTF), by Gene Signature

  During the entire study, up to 5 years

Study Arms (1)

Group A

EXPERIMENTAL

All patients are to receive the same treatment consisting of 24 injections of the immunotherapeutic GSK2132231A combined with a course of 8 cycles of dacarbazine given at the beginning of the treatment

Biological: Immunotherapeutic GSK2132231A; Drug: Dacarbazine

Interventions

Immunotherapeutic GSK2132231A BIOLOGICAL

Intramuscular administration

Group A

Dacarbazine DRUG

Intravenous administration Chemotherapy

Also known as: DTIC, Imidazole Carboxamide, DTIC-Dome

Group A

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 patient with histologically proven, measurable metastatic cutaneous melanoma
• Written informed consent has been obtained from the patient before the performance of any 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 MAGE-A3 antigen, detected by Reverse-Transcription Polymerase Chain Reaction (RT-PCR).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• The patient has normal organ functions.
• 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.
• In the view of the investigator, the patient can and will comply with the requirements of the protocol.

You may not qualify if:

• The patient has at any time received systemic (bio)-chemotherapy.
• 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.
• The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
• The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen or any cancer immunotherapeutic for his/her metastatic disease.
• 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.
• 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.
• History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
• 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 (HIV).
• 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.
• The patient has an uncontrolled bleeding disorder.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

GSK Investigational Site

Brussels, 1090, Belgium

Location

GSK Investigational Site

Brussels, 1180, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Liège, 4000, Belgium

Location

GSK Investigational Site

Roeselare, 8800, Belgium

Location

GSK Investigational Site

Yvoir, 5530, Belgium

Location

GSK Investigational Site

Caen, 14033, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Paris, 75475, France

Location

GSK Investigational Site

Reims, 51092, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

Related Publications (1)

• 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.

  PMID: 29177094 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Dacarbazine

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

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: February 24, 2009
• Study Start: May 26, 2009
• Primary Completion: November 17, 2014
• Study Completion: November 17, 2014
• Last Updated: July 12, 2017
• Results First Posted: March 30, 2017

Record last verified: 2017-06

Locations

BE (6); FR (8)