NCT01460888Unknown1 期
Radiotherapy & Olaparib in COmbination for Carcinoma of the Oesophagus. A Phase I Trial.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer
研究概览
简要总结
The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer who are unsuitable for platinum containing chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically confirmed adenocarcinoma or squamous cell carcinoma of the oesophagus including Siewert type 1 or 2 tumours with ≤2cm gastric mucosal extension
- •Unsuitable for radical chemoradiation therapy but suitable for radiotherapy
- •Total length of tumour and involved lymph nodes ≤10cm
- •No oesophageal stent in situ
- •No previous chemotherapy or radiotherapy for oesophagus cancer
- •Disease which can be encompassed within a radical radiotherapy treatment volume
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see ECOG criteria appendix 1)
- •Provision of fully informed consent, signed, written and dated, prior to any study specific procedures.
- •> 18 years of age.
- •Adequate organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
- •Haemoglobin ≥ 10.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •White blood cells (WBC) > 3 x 109/L
- •Platelet count ≥ 100 x 109/L
- •No dysplastic features on peripheral blood smear
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal
- •Aspartate aminotransferase (AST(SGOT)/Alanine transaminase (ALT)SGPT) ≤ 2.5 x institutional upper limit of normal
- •Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
- •Adequate lung function: no history of interstitial lung disease and FEV1 > 1litre and >30% predicted.
- •Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day
- •Postmenopausal is defined as:
- •Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
- •Luteinizing hormone(LH) and Follicle-stimulating hormone (FSH) levels in the post menopausal range for women under 50,
- •radiation-induced oophorectomy with last menses >1 year ago,
- •chemotherapy-induced menopause with >1 year interval since last menses,
- •surgical sterilisation (bilateral oophorectomy or hysterectomy).
- •Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- •Fit to receive all study treatments
- •Swallowing sufficiently good to tolerate oral medication
- •Life expectancy ≥ 4 months.
排除标准
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Previous enrolment in the present study
- •Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
- •Any previous treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, including olaparib.
- •Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
- •Patients receiving the following classes of inhibitors of cytochrome P450 3A4 (CYP3A4)
- •Azole antifungals
- •Macrolide antibiotics
- •Protease inhibitors
- •Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- •Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, or any psychiatric disorder that prohibits obtaining informed consent.
- •Patients with a history of interstitial lung disease, inflammatory lung conditions, or severe chronic obstructive pulmonary disease (COPD) (FEV1<1litre or < 30% predicted). Patients with pneumonia within the previous 3 months.
- •Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •Patients with oesophageal stent in-situ
- •Patients with myelodysplastic syndrome/acute myeloid leukaemia
- •Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- •Patients with known active hepatic disease (i.e., Hepatitis B or C).
- •Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- •Patients with uncontrolled seizures.
- •Concurrent uncontrolled medical illness, or other previous or current malignant disease likely to interfere with protocol treatments / comparisons
- •Any pregnant, lactating women or potentially childbearing patients not using adequate contraception (see section 3.4 for details of required contraception).
- •Previous chemotherapy or radiotherapy for oesophageal cancer
- •Metastatic disease apart from local lymph node disease which can be reasonably encompassed within the radiotherapy volume (total length of tumour and lymph node disease should be <10cm)
- •ECOG performance status >2
研究组 & 干预措施
OLA-0 (de-escalation dose)
Experimental
25mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Olaparib (Drug)
OLA-0 (de-escalation dose)
Experimental
25mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Radical external beam radiotherapy, 50Gy in 25 fractions (Radiation)
OLA-1
Experimental
50mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Olaparib (Drug)
OLA-1
Experimental
50mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Radical external beam radiotherapy, 50Gy in 25 fractions (Radiation)
OLA-2
Experimental
100mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Olaparib (Drug)
OLA-2
Experimental
100mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Radical external beam radiotherapy, 50Gy in 25 fractions (Radiation)
OLA-3
Experimental
200mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Olaparib (Drug)
OLA-3
Experimental
200mg olaparib twice daily + radiotherapy (50Gy in 25 fractions)
干预措施: Radical external beam radiotherapy, 50Gy in 25 fractions (Radiation)
RT alone
Active Comparator
干预措施: Radical external beam radiotherapy, 50Gy in 25 fractions (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of olaparib in combination with radical radiotherapy in patients with oesophageal cancer
时间窗: 3 months post treatment
MTD will be determined by the number of patients experiencing dose limiting toxicities (DLTs) in each treatment cohort, using a 3+3 dose escalation schedule. A DLT is determined as grade 4 oesophagitis or dysphagia, or any other grade 3 toxicity. DLTs will be assessed weekly during treatment (day -3 to week 5), 10-14 days after completing treatment, weekly for a further 3 weeks and 3 months after completing treatment.
次要结局
- Radiotherapy (RT) compliance(At completion of RT treatment (end of week 5))
- Olaparib compliance(At completion of olaparib treatment (end of week 5))
- Overall toxicity profile of treatment (NCRI Common Toxicity Criteria for Adverse Effects V3)(Assessed at all study visits, up to 3 years post treatment.)
- Exploration of blood and tissue borne pharmacodynamic markers to establish the biological efficacy of the addition of Olaparib to radiotherapy.(Up to 3 months post treatment)
- Local and overall treatment failure rate(3 months)
研究者
研究点 (2)
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