How To Evaluate The Efficiency And Safety Of Neoadjuvant Chemotherapy In Locally Advanced Cancer Cervix

Study Overview
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Brief Summary
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This strategy might suggest a therapeutic option to preserve ovarian function in young patients among which locally advanced cancer cervix is common. Based on previous studies, neoadjuvant irinotecan and cisplatin followed by radical hysterectomy and adjuvant chemotherapy has the potential to improve the prognosis compared the concurrent chemo-radiotherapy(CCRT). To offer an alternative effective treatment line replacing concurrent chemo-radiotherapy to avoid dramatic radiotherapy induced complications which might impede a safe successful surgery. 2- To reduce the proportion of patients who will go for radiotherapy, consequently those patients will still have a chance of probable less complicated surgery in case of local recurrence. 3- This study will involve neo-adjuvant chemotherapy (NACT) in treating patients with stage II-III cervical cancer for reducing tumor size, minimizing blood loss during surgery and eradication of possible micro-metastasis. 4- To Improve the likelihood of achieving complete tumor resection after NACT. 5- Investigators will further follow-up those patients for more detailed assessments to confirm whether NACT can improve patients' prognoses, survival, quality of life, and the standard of care.

Detailed Description
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Treatments for locally advanced cervical cancer, defined as International Federation of Gynecology and Obstetrics (FIGO) stage Ib2-III include primary surgery, neoadjuvant chemotherapy and concurrent chemo-radiotherapy (CCRT). In many countries, CCRT is accepted as the standard therapy for such tumors. However, each of these therapies has both advantages and disadvantages, however, more recently it has been given using neoadjuvant chemotherapy with intravenous irinotecan hydrochloride (CPT-11) and cisplatin. DNA topoisomerases are enzymes that regulate and control DNA topology. Topoisomerase 1 catalyzes the transient cutting of a single DNA strand, the passage of another DNA strand through the break and then resealing of the DNA break. Camptothecin (CPT), an antitumor alkaloid isolated from Camptotheca acuminata, interferes with DNA topoisomerase 1 function. Cisplatin (cis-dichlorodiammineplatinums II) is a first generation platinum compound. Platinum-based NACT followed by radical hysterectomy has been proposed as an alternative approach to radiotherapy or CCRT in locally advanced cervical cancer, especially of squamous cell histology, with objective response rates ranging from 69.4% to 90.2%, pathological optimal response rates ranging from 21.3% to 48.3%, 5-year disease free survival (DFS) rates ranging from 55.4% to 71% and 5-year overall survival(OS) rates ranging from 58.9% to 81%, respectively.

Official Title
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Phase II Trial To Evaluate The Efficiency And Safety Of Neoadjuvant Chemotherapy In Locally Advanced Cancer Cervix

Conditions
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Locally Advanced Cervical Carcinoma

Intervention / Treatment
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* Drug: Cis Platinum + Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 - Patients with histologically confirmed invasive squamous cell carcinoma of the uterine cervix; (ii) FIGO stage system (2018 version): stage II-III 2- No previous treatment. 3- patients with age of 20-75 years at enrollment. 4- Eastern Cooperative Oncology Group performance status (PS) of 0 or 1. 5- Preserved function of major organs (bone marrow, heart, liver and kidney) 6- Lab values within specified ranges, including a neutrophil count greater than 2000/μL, a platelet count greater than 100 000/ mm3 , a hemoglobin level greater than 9.0 g/dL (values after blood transfusion are accepted), levels of aspartate aminotransferase and alanine aminotransferase less than 100 IU/L, a total bilirubin level less than 1.5 mg/dL, a serum creatinine level less than 1.5 mg/dL, creatinine clearance greater than 60 mL/ min. Exclusion Criteria: : Distinct evidence of infectious disease. Serious concurrent disease (cardiac disease, uncontrolled diabetes mellitus, malignant hypertension and a bleeding tendency). Pregnant women, or women who want to become pregnant. History of serious drug hypersensitivity or drug allergy.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm of patients with locally advanced cancer cervix<br>Single arm study to assess the efficacy and safety of use of neoadjuvant cisplatin and irinotecan in treatment of patients with locally advanced cancer cervix. A combined regimen of intravenous infusion of cisplatin 80mg/m2 on day 1 with irinotecan 60mg/m2 on day 1 and day 8 of every 21- day cycle for 3 cycles. Then, MRI pelvis will be used for assessment of disease response. According to RECIST criteria, patients who will develop at least stable disease, will be sent for radical hysterectomy. Afterwards, 6 weeks after the surgery, another 3 cycles of the same regimen will be given to the participants as adjuvant treatment. | Drug: Cis Platinum + Irinotecan<br>* Studying the efficacy and safety of neoadjuvant cisplatin and irinotecan use in treatment of locally advanced cancer cervix.<br>* Other names: No other interventions, investigators are trying only one intervention to test if it could be an alternative effective line for treating the patients with locally advanced cancer cervix.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respectability of the tumor | Evaluation of the effect of use of neoadjuvant cisplatin and irinotecan on the tumor size when assessed by MRI pelvis cancer Evaluation of the tumor size by MRI pelvis after giving 3 cycles of cisplatin and irinotecan. So, baseline( prechemotherapy) MRI pelvis and another re-evaluation MRI pelvis will be used for proper assessment. | Evaluation will be done by MRI pelvis after 3 cycles( of the 21- day cycle) of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2- year relapse free survival(RFS) | Evaluation of the effect of use of neoadjuvant cisplatin and irinotecan on the 2- year RFS of patients with locally advanced cancer cervix | 2 years | 
| 2- year overall survival(OS) | Evaluation of the effect of use of neoadjuvant cisplatin and irinotecan on the 2- year OS of patients with locally advanced cancer cervix | 2 years | 
| Toxicity profile | Investigators will assess the incidence of treatment related adverse events ( e.g neutropenia,mucositis,renal insufficiency, neuropathy, nausea and vomiting)and its severity on the CTCAE scale of 5 grades ( mild,moderate,severe,life- threatening, and death related to AE. ) | 2 years |