Study of GSK2241658A Antigen-Specific Cancer Immunotherapeutic in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 25
- 主要终点
- Number of Patients With Severe Toxicities During the Study Treatment Period
研究概览
简要总结
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.
详细描述
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.
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, 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
- •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.
排除标准
- •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.
研究组 & 干预措施
NY-ESO 1 Group
Patients with non-operable and progressing metastatic cutaneous melanoma, received up to 24 doses of GSK2241658A Cancer Immunotherapeutic, provided that at each tumor evaluation time point, the clinical criteria to continue the treatment were met, including patients having a clinical response.
干预措施: GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI) (Biological)
结局指标
主要结局
Number of Patients With Severe Toxicities During the Study Treatment Period
时间窗: During the study treatment period (maximum duration = 49 months).
Severe toxicity was defined, according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), as 1)an Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly related Grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy to be taken into account and as 2)an ASCI related or possibly related Grade 2 or higher allergic reaction occurring within 24 hours of the dose administration.
Number of Patients With the Best Overall Response in the Overall Population
时间窗: During the study treatment period (maximum duration = 49 months).
Best response was recorded from the start of treatment until disease progression. Response assessment was essentially based on a set of measurable lesions (target lesions \[TL\]), and any other lesions (non-target lesions \[NTL\]), both identified at baseline. Complete Response (CR)=disappearance of all TL or NTL; Partial Response (PR) = at least 30 percent (%) decrease in the sum of the longest diameter(LD) of TL compared to baseline, stable disease (SD) = neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for Progressive disease (PD) compared with baseline; PD = at least 20% increase in the sum of LD of TL compared with baseline, or the appearance of one or more new lesions, or both of these, and/or unequivocal progression of existing NTL; NE =non-evaluable; Clinical response: any CR or PR best overall response; Disease control: any CR, PR, SD or SD/PR best overall response.
Number of Patients With Severe Toxicities During the Follow-up Period
时间窗: During the one year follow-up period (i.e. from Month 49 until Month 61)
Severe toxicity was defined, according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), as 1)an Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly related Grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy in order to be taken into account and as 2)an ASCI related or possibly related Grade 2 or higher allergic reaction occurring within 24 hours of the dose administration. All active follow-up visits and procedures were stopped, hence this follow-up analysis was not performed as initially planned.
次要结局
- Number of Patients With Best Overall Response Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria(During the study treatment period (maximum duration = 49 months).)
- 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(After 12, 22, 31 and 54 weeks of treatment.)
- Overall Survival (OS)(From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49))
- Number of Patients With Adverse Events (AEs) by Maximum Grade(During the study treatment period (maximum duration = 49 months).)
- Progression-free Survival (PFS) Rate(From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49))
- Cell Mediated Immune Response for Anti-NY-ESO-1 Antibodies (T-cell)(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))
- Number of Patients With Serious Adverse Events (SAEs) by Maximum Grade(During the study treatment period (maximum duration = 49 months).)
- Time to Treatment Failure (TTF)(From first treatment administration (i.e. at Week 0) until the last treatment administration (i.e. at Month 48))
- The Duration of Response for Patients With CR, PR or Stable Disease (SD) Status(From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49))
- Number of Patients With Progression-free Survival Events(From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49))
- 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(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.])
- Anti NY-ESO-1 Antibody Concentrations(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))
- Number of Patients With Adverse Events (AEs) That Are Causally Related to Treatment Administration by Maximum Grade(During the study treatment period (maximum duration = 49 months).)
- Humoral Response for Anti NY-ESO-1 Antibodies(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))
- Number of Patients With Serious Adverse Events (SAEs) That Are Causally Related to Treatment Administration by Maximum Grade(During the study treatment period (maximum duration = 49 months).)