Phase 2, Randomized, Open Label, Multicenter Study of Intradermal IMA901 Plus GM-CSF With or Without Low Dose Cyclophosphamide Pre-treatment in Advanced Renal Cell Carcinoma Patients With Measurable Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 44
- 主要终点
- Disease control rate
研究概览
简要总结
This study was conducted in order to evaluate the efficacy and safety of the cancer vaccine IMA901 and GM-CSF as adjuvant in the treatment of advanced renal cell carcinoma.
Patients received vaccination with GM-CSF followed by IMA901 during the study period of 9 months. Patients received pre-treatment with a single i.v. infusion of cyclophosphamide prior to the first vaccination.
详细描述
This is a multicenter, open label, randomized phase 2 study which investigated the effect of a second-line systemic treatment with IMA901 plus GM-CSF in RCC patients. Randomization was done according to a pre-treatment with low-dose cyclophosphamide (CY). Secondary endpoints comprised tumor response parameters.
The study population consisted of HLA-A*02-positive men or women with advanced RCC of the clear-cell type classified as having a favorable or intermediate risk after first-line systemic therapy for. Patients had to be aged 18 years or older, had at least have one measurable tumor lesion and had have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease, during or after which the patient had experienced disease progression.
Patients in both arms received a total of 17 vaccinations with GM-CSF followed by IMA901 during the 9 month treatment period.
At screening baseline tumor status was assessed by CT or MRI. During the study tumor assessments were performed every 6 weeks.
Immunomonitoring (T-cell responses to peptides contained in IMA901 and analysis of other immune cell populations that may influence T-cell responses), serum levels of antibodies and molecules with suspected influence on immune response were assessed on several occasions during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Aged at least 18 years
- •HLA type: HLA-A*02-positive
- •Histologically documented advanced clear-cell RCC
- •Patients who have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease systematic therapy for advanced disease and must be candidates for second-line therapy (NOTE: in Germany and Austria only patients after first-line tyrosine kinase inhibitor failure will be included into the study)
- •Patients having experienced documented tumor progression
- •At least one unidimensional measurable target lesion
- •Karnofsky Performance Status ≥ 80%
- •Favorable or intermediate risk according to the 3-score MSKCC criteria.
- •Able to understand the nature of the study and give written informed consent
- •Willingness and ability to comply with the study protocol for the duration of the study
排除标准
- •Poor risk according to the 3-score MSKCC criteria
- •Immunosuppressive therapy within 4 weeks before study entry, e.g. corticosteroid treatment
- •History of other malignant tumors, except non-melanoma-skin cancer or curatively excised cervical carcinoma in situ
- •Presence of brain metastases on MRI or CT scan
- •Patients with a history or evidence of systemic autoimmune disease
- •Any vaccination in the two weeks before study entry
- •Any planned prophylactic vaccination from study entry until the end of the induction period (5 weeks after the first vaccination)
- •Known active hepatitis B or C infection
- •Known HIV infection
- •Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues.
- •Any of the following in the 4 weeks before study entry:
- •Major surgery
- •Anticancer treatments including (but not limited to) cytotoxic chemotherapy, radiotherapy, immunotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies
- •Unresolved toxicity from prior anticancer treatments including (but not limited to) cytotoxic chemotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies, radiotherapy, or immunotherapy
- •Received study drug within any clinical study
- •Any of the following abnormal laboratory values:
- •Hematology: Hb < 9 g/dL; WBC < 3 x 109/L; neutrophils < 1.5 x 109/L; lymphocytes < 1.0 x 109/L; platelets < 100 x 109/L
- •Liver function: serum bilirubin > 1.5 x upper normal limit (unless a history of Gilbert's disease); ALAT or ASAT > 3 x upper normal limit (>5 x upper normal limit if liver metastases are present)
- •Renal function: serum creatinine > 200 µmol/L
- •Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, for example:
- •Heart failure or non compensated active heart disease
- •Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension
- •Symptomatic neurotoxicity (motor or sensory) ≥ grade 2 National Cancer Institute - Common Toxicity Criteria (NCI-CTC).
- •Severe pulmonary dysfunction
- •Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator's opinion
- •Active infections requiring oral or intravenous antibiotics
- •Women or men who decline to practice a medically approved method of contraception
- •Pregnancy or breastfeeding
- •Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study
研究组 & 干预措施
1
Pre-treatment with a single low dose of Cyclophosphamide followed by IMA901 vaccination plus GM-CSF as adjuvant
干预措施: Endoxana, IMA901, Leukine (Drug)
2
No pre-treatment with Cyclophosphamide before vaccination with IMA901 and GM-CSF as adjuvant
干预措施: IMA901 and Leukine (Drug)
结局指标
主要结局
Disease control rate
时间窗: after 26 weeks
次要结局
- Effect of cyclophosphamide pre-treatment on immune response(Visit C, 1, 5,6,7, 10, 14)
- Tumor response rates and SD rate(after 26 and 38 weeks)
- Duration of response(from the time response is first documented until the first date of recurrence or PD)
- Time to response(From Visit c to PR or CR)
- TTP(From visit C to until tumor progression)
- PFS and OS(From visit C to tumor progression or death)
- DCR(after 38 weeks on study)
- Immune response(Visit C, 1, 5, 6, 7, 10 and 14)
- Safety(From inclusion on the study until 3 weeks after end of study visit)