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

Phase 2TerminatedNCT00849875

GlaxoSmithKline48 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma

Interventions

Immunotherapeutic GSK2132231ABIOLOGICAL

Intramuscular administration

DacarbazineDRUG

Intravenous administration Chemotherapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (14)

GSK Investigational Site

Brussels, Belgium

GSK Investigational Site

Brussels, Belgium

GSK Investigational Site

Brussels, Belgium

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Post Dose 4 at Week 13 (W13).

Data from ClinicalTrials.gov

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Secondary Outcomes

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

Response assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs), and followed up until disease progression. Up to 5 MLs per organ \& 10 in total were identified as TLs and measured at baseline, selected based on size (those with the longest diameter \[LD\]) and measurability; a sum of LDs for all TLs was calculated and reported as baseline sum LD, which was used to characterize objective tumor response (OR), OR being defined as either complete response (CR) and/or partial response (PR) post MAGE-A3 ASCI treatment. After identification, MLs and TLs were assessed as regards CR and PR definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria: CR = Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis; PR = At least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.