Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Association With Chemotherapy in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Patients Reported With Unsolicited Adverse Events (AEs) That Were Causally Related to Treatment Administration by Maximum Grade.
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Group A
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
干预措施: Immunotherapeutic GSK2132231A (Biological)
Group A
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
干预措施: Dacarbazine (Drug)
结局指标
主要结局
Number of Patients Reported With Unsolicited Adverse Events (AEs) That Were Causally Related to Treatment Administration by Maximum Grade.
时间窗: Within the 31-day (Days 0-30) post-administration period.
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.
Number of Patients Reported With Serious Adverse Events (SAEs)
时间窗: During the entire study period, up to 5 years
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.
Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3)
时间窗: Post Dose 4 at Week 13 (W13).
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.
Anti-MAGE-A3 Antibody Concentrations
时间窗: Post Dose 4 at Week 13 (W13).
Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL)
Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies
时间窗: Post Dose 4 at Week 13 (W13).
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
Anti-MAGE-A3 Antibody Concentrations (CMI)
时间窗: Post Dose 4 at Week 13 (W13).
Analysis of MAGE-A3 cellular response was not performed and data were not collected..
Concentrations of Antibodies Against Protein D (Anti-PD)
时间窗: Post Dose 4 at Week 13 (W13).
Anti-PD antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL).
Number of Patients With Treatment Response for Anti-PD
时间窗: Post Dose 4 at Week 13 (W13).
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
次要结局
- 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)
- Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade.(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)
- Progression-free Survival (PFS) for the Overall Population(During the entire study, up to 5 years)
- Progression-free Survival (PFS) by Gene Signature(During the entire study, up to 5 years)
- Progression-free Survival (PFS) After Slow Progressive Disease (SPD) by Gene Signature(During the entire study, up to 5 years)
- Overall Survival (OS) by Gene Signature(During the entire study, up to 5 years)
- Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Gamma-glutamyl Transpeptidase (GGT) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hypercalcemia (HCA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hyperkalemia (HKA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hypernatremia (HNA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hypoalbuminemia(hAL) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hypocalcemia(hCA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hypokalemia (hKA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Hyponatremia (hNA) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Abnormal Partial Thromboplastin Time (PTT) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Any Adverse Events (AEs) and With AEs by Maximum Grade(Within the 31-day follow-up period post treatment administration.)
- Number of Patients With Abnormal Platelets(PLT) Values by Maximum Grade(During the entire study, up to 5 years)
- Number of Patients With Any Serious Adverse Events (SAEs) and With AEs by Maximum Grade(Within the 31-day follow-up period post treatment administration.)