A Randomised, Double-blind, Placebo-controlled, Phase I/II Trial of RNActive®-Derived Cancer Vaccine (CV9104) in Asymptomatic or Minimally Symptomatic Patients With Metastatic Castrate-refractory Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- CureVac
- 入组人数
- 197
- 试验地点
- 96
- 主要终点
- Phase I (Safety Lead-In): Occurrence of dose-limiting toxicity (DLT) during the first 4 weeks of treatment (after administration of 3 vaccinations and after a 1 week observation period
研究概览
简要总结
The purpose of this study is to determine whether the new RNActive®-derived prostate cancer vaccine CV9104 prolongs survival in patients with asymptomatic or minimally symptomatic metastatic prostate cancer that is castrate resistant.
详细描述
The study is the first clinical study with the new prostate cancer vaccine CV9104. This vaccine is composed of 6RNActive®-based compounds, each encoding for an antigen that is overexpressed in prostate cancer compared to healthy tissues. RNActive®-based vaccines are a novel class of vaccines based on messenger RNA.
The study is a double-blind randomized placebo-controlled phase I/II trial in men with asymptomatic- minimally symptomatic metastatic castrate-refractory prostate cancer.
The phase 1 (safety lead- in) part of the trial has the primary objective to assess the safety of CV9104 and to determine the dose for the randomized phase II part.
The primary objective of the phase II part is to compare overall survival in patients treated with CV9104 compared to patients treated with placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, age ≥18 years
- •Histologically confirmed castrate refractory metastatic adenocarcinoma of the prostate with progressive disease after surgical castration or during androgen suppression therapy including a GNRH agonist or antagonist and after at least 1 additional anti-hormonal manipulation; and serum testosterone level of < 50 ng/dL or < 1.7 nmol/L
- •Progression will be confirmed either
- •radiologically or
- •by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and a PSA > 2 ng/mL.
- •An antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy for at least 6 weeks.
- •Metastatic disease confirmed by imaging
- •ECOG performance status 0 or 1
排除标准
- •Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
- •Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
- •Systemic treatment with immunosuppressive agents
- •Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
- •History of or current autoimmune disorders
- •Primary or secondary immune deficiency.
- •Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
- •Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to WHO criteria or uncontrolled hypertension at the time of enrolment (systolic blood pressure ≥ 180 mm Hg)´
- •Previous chemotherapy for metastatic PCA.
- •Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
- •Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
- •Presence of visceral metastases.
- •History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).
结局指标
主要结局
Phase I (Safety Lead-In): Occurrence of dose-limiting toxicity (DLT) during the first 4 weeks of treatment (after administration of 3 vaccinations and after a 1 week observation period
时间窗: Up to 4 weeks
Safety Lead in Portion: Patients will receive CV9104 at a starting dose of 1920 µg in weeks 1, 2 and 3. Safety lead-in patients will be observed for DLTs until 1 week after Vaccination 3 (week 4). In case no DLTs will be observed vaccinations will continue in weeks 5, 7, 9, 12, 15, 18 and 24, then every 6 weeks for up to 12 months after the first vaccination and then every 3 months thereafter until one of the criteria for study treatment discontinuation is met
Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years.
时间窗: Overall survival will be assessed during the lifetime of the study
次要结局
- Progression free survival from date of randomisation(Every 3 months for up to 2 years)
- Cellular and humoral immune response rate against the 6 antigens encoded by CV9104(Immune responses will be assessed at baseline, in week 6 and week 24 after start of vaccination)
- Progression free survival from randomisation until second progression on first subsequent therapy(Every 3 and 6 months up to 2 years)
- Absolute change and area under the curve from baseline EQ-5D score and pain sub-score(Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years)
- Progression free survival from start of first subsequent systemic therapy(Every 6 months until 2 years)
- Percent change to maximal and to minimal PSA from baseline and before start of first subsequent systemic cancer therapy and from start of first systemic therapy to end of first subsequent systemic therapy(Every 3 months up to 2 years)
- Time to symptom progression based on FACT P score and subscores(Assessments at baseline, weeks 5, 9,18, 24 and every 3 months for up to 2 years)