Cervical cancer tumor micro-environment immune-profiling and effect on early response to standard chemoradiotherapy in Indian patients
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- AIIMS
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- a.Categorize locally advanced cervical cancers into immune inflamed and immune suppressed based on immune cell infiltration
研究概览
简要总结
Cervical cancer isthe most common cancer among females in rural India. The standard treatment ischemo-radiotherapy. Five year survival remains around 50% only in locallyadvanced cervical cancer with most patients recurring within the initial 2years. Immune evasion by various mechanisms is one of the ways of resistance totreatment in various cancers. Immune profiling of tumour micro-environment(TME) before treatment will help identify tumours that are inherentlyimmunosuppressed and therefore expected to have poor responses to standardanti-cancer treatment. This immune profiling will also help in future to conducttrials using hypofractionated (> 5 Gy/ fraction) radiotherapy to make theTME immune-inflamed. In the proposed pilot study, 60 patients oflocally advanced (Stage IB2 – IIIB) cervical cancer will be recruited forimmunoprofiling and will be treated with standard chemoradiation followed bybrachytherapy. Paraffin embedded primary tumour biopsy will be subjected toimmunohistochemistry (IHC). IHC for CD8 and regulatory T cell infiltration intumour (CD4 and FOXP3) will be performed. Similarly M2 macrophages will beidentified by IHC for CD 68. Early clinical response will be assessed at theend of external beam radiotherapy and 3 months after completion ofbrachytherapy. Progression free survival at 18 and 24 months will be noted andcorrelated with the immune profile of pretreatment biopsy. Clinical responseswill be graded as progressive disease, stable disease, partial response andcomplete response. Uni-variate analysis by log rank test for survival data willbe attempted.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.FIGO 2008 stage IB2, IIB, IIIB disease. 2.Age 18 years or older and <65 years 3.ECOG performance status
- •2 4.Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adeno-squamous cell carcinoma of the cervix 5.HB> 9 g/dL; ANC > 1000 / mm3; Plt > 1,00,000/ mm3 6.Bilirubin ≤ 1.5 x ULN , AST or ALT ≤ 2.5 x ULN 7.Adequate renal function: creatinine ≤ ULN (CTC Grade 0) or calculated creatinine clearance (Cockcroft-Gault Formula) ≥ 60ml/min or ≥ 50 ml/min by EDTA creatinine clearance 8.Written informed consent.
排除标准
- •1.Any previous pelvic radiotherapy 2.Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven or ≥ 10 mm short axis diameter on CT) 3.FIGO STAGE IIIA 4.Patients assessed at presentation as requiring interstitial brachytherapy treatment 5.Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria 6.Evidence of metastases 7.Diagnosis of Crohn’s disease or ulcerative colitis 8.Peripheral neuropathy > grade 2 (as per CTCAE) 9.Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervix cancer therapy 10.Patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last 5 years 11.Patients who are pregnant or lactating 12.Any contraindication to cisplatin 13.Serious uncontrolled medical condition 14.HIV positive.
结局指标
主要结局
a.Categorize locally advanced cervical cancers into immune inflamed and immune suppressed based on immune cell infiltration
时间窗: Eighteen months and 24 months
b.Tumour micro-environment inflammatory cells immune profiling
时间窗: Eighteen months and 24 months
c.Evaluate response rates to standard chemoradiotherapy and progression free survival versus immune cell infiltration
时间窗: Eighteen months and 24 months
次要结局
- N/A(N/A)