Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Phase I: the recommended safe dosing for the combination of chemoradiation with gemcitabine plus panitumumab.
研究概览
简要总结
The purpose of this study is to investigate whether the addition of panitumumab to radiotherapy plus gemcitabine will increase the number of patients who are alive and progression free at 7 months.
详细描述
This is a phase I/II, multi-center dose escalation study.
Phase I:
Patients will be enrolled in cohorts of 3 per dose level until the MTD of panitumumab has been established.
Phase II:
Up to approximately 56 patients will be treated at the MTD level of panitumumab as established in the phase I part of the study.
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
- •Histological or cytological confirmed pancreatic cancer.
- •Not eligible for curative resection.
- •No distant metastases present.
- •Previously untreated with chemotherapy and anti-cancer biologicals for current malignancy.
- •No other current malignant disease, except for basal cell carcinoma of the skin.
- •Measurable or evaluable disease as defined by RECIST 1.1 criteria.
- •Performance status 0-2 Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Scale.
- •Age ≥ 18 years.
- •Adequate haematological and biological functions:
- •Bone marrow function:
- •Neutrophils ≥ 1.5 x 109/L
- •Platelets ≥ 100 x 109/L
- •Hb ≥ 6 mmol/L
- •Hepatic function:
- •AST/ALT and alkaline phosphatase (ALP) ≤ 2.5 x institutional upper limit of normal (ULN)
- •Bilirubin ≤ 1.5 times institutional ULN
- •Renal function:
- •eGFR >50ml/min
- •Metabolic Function:
- •Magnesium ≥ lower limit of normal
- •Calcium ≥ lower limit of normal.
- •No imminent bowel obstruction.
- •No active bleeding.
- •No uncontrolled infection.
- •Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.
- •Signed informed consent.
排除标准
- •Participation in another therapeutic clinical study within 30 days of enrollment or during this clinical study.
- •No adequate radiation therapy possible: based on the opinion of the radiation oncologist when radiation therapy cannot be performed because radiation field is too large (PTV volume too large or OAR too high)
- •History of allergic reactions to gemcitabine or antibody treatment.
- •Presence of any serious concomitant systemic disorders incompatible with the clinical study (e.g. uncontrolled inter-current illness including ongoing or active infection, uncontrolled hypertension).
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 1 year before enrolment/randomization
- •History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
- •Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance.
- •Pregnant or breastfeeding women.
- •Absence of adequate contraception for both male and female fertile patients for the duration of the study; and also for six months after last treatment.
- •Known positive status for HIV and/or hepatitis B or C.
- •Any reason why, in the investigator's opinion, the patient should not participate in the study.
- •Drug or alcohol abuse.
研究组 & 干预措施
Panitumumab
干预措施: Panitumumab (Drug)
结局指标
主要结局
Phase I: the recommended safe dosing for the combination of chemoradiation with gemcitabine plus panitumumab.
时间窗: 43 days
During the phase I part of the study, we have planned to study four dose levels of panitumumab if no MTD is being derived before the final dose level. Patients will be enrolled in cohorts of 3 per dose level. If there are no dose-limiting toxicities (DLTs) experienced by the first 3 patients in a cohort during the first 43 days after the first study treatment, additional patients will be entered in the next dose level. At the final dose level recommended for the phase II study a minimum of 6 patients will be treated.
Phase II: safety and tolerability
时间窗: 1 year
Toxicities will be tabulated and summarized overall and across grade and type according to CTC criteria. When grade ≥3 toxicity occurs in ≥ 50% of patients this will be evaluated as unacceptable toxicity according to the two step evaluation design as described. This relatively high percentage of toxicity is based on the details of multiple studies of combination chemoradiation with gemcitabine as given in the introduction.
Phase II: the proportion of patients that is alive and progression-free at 7 months.
时间窗: 1 year
For each patient, the time of progression will be recorded. Any patient who discontinues treatment due to adverse reactions, refusal, or who goes on to receive alternate therapy will be considered censored at their last tumor assessment. The sample size was determined based upon a Bryant Day Phase II clinical trial design, taking into account both activity as well as toxicity. The proportion of patients with 7 month PFS will be calculated with exact 95% confidence intervals.
次要结局
- Early signs of clinical activity of the combination of chemoradiation with gemcitabine plus panitumumab.(1 year)
- Clinical response rate of the combination of chemoradiation with gemcitabine plus panitumumab.(1 year)
- Time-to-progression (TTP) and overall survival(1 year)
研究者
H.M.W. Verheul
Prof. Dr.
Amsterdam UMC, location VUmc