Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility

Study Overview
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Brief Summary
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If no metastases are observed, patients will start a short protocol of four courses of weekly neo-adjuvant chemotherapy (12 weeks). If response to chemotherapy results in a tumor of less than 2 cm, cervical conisation will be performed.

Detailed Description
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The standard treatment of stage Ib1 2-4 cm cervical cancer in women who wish to preserve fertility is an abdominal radical trachelectomy with pelvic lymph node dissection. Since the number of take home babies after completing this procedure is below 10%, there is a need for exploration of alternative treatment modalities with better chances of preserving fertility at equal risk of recurrence. Since low fertility rates after abdominal radical hysterectomy are observed due to the radical surgery performed on the uterine cervix, less radical surgery is warranted. To enable less radical surgery by cervical conisation, neo-adjuvant chemotherapy to reduce tumor size is incorporated to the multi-modal treatment scheme of these patients.

Official Title
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Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Carboplatin
* Procedure: conisation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage Ib1 cervical cancer measuring ≥2 - ≤4 cm on physical examination and imaging in any direction Histologic type: squamous cell carcinoma (SCC), adeno cell carcinoma (ACC), adeno-squamous cell carcinoma (ASC) Lymph vascular space invasion allowed (LVSI) Age ≥18 years and ≤ 40 years Wish to preserve fertility Written and signed informed consent Negative serum or urine pregnancy test within 14 days prior to registration, and an effective method of contraception must be used during treatment MRI abdomen and pelvis, chest X-ray must be performed and negative for metastatic disease within 12 weeks of enrolment No metastases on pelvic lymph node dissection Laboratory values: serum creatinine < 140 μmol/L; creatinine clearance > 60 ml/min(Cockroft formula); white blood cell count > 3.5 x 109/l; platelets > 100 x 109 /l Exclusion Criteria: Other high grade histologies like neuro-endocrine and clearcell carcinoma FIGO stage Ia, Ib1< 2 cm, Ib2, II, III and IV disease Involvement of tumor in uterine corpus on MRI or hysteroscopy if performed Evidence of metastatic disease on imagining (PET/CT/MRI) performed within 12 weeks of enrolment other malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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
Interventional Model Description: One arm two-stage Simon's design with response to neo-adjuvant chemotherapy as the primary endpoint
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neo-adjuvant chemotherapy<br>The patients are given weekly paclitaxel 80 mg/m2 + carboplatin AUC=2 (or AUC=6 per three weeks) during 12 weeks/4 courses followed by conization if tumor size is reduced to <2 cm | Drug: Paclitaxel<br>* weekly paclitaxel 80 mg/m2 for 12 weeks<br>Drug: Carboplatin<br>* weekly carboplatin AUC=2 for 12 weeks<br>Procedure: conisation<br>* if tumor is reduced to <2 cm, patients will be treated with a conisation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of neo-adjuvant chemotherapy | efficacy of neo-adjuvant chemotherapy on tumor response | week 6 of neoadjuvant treatment | 
| safety of neo-adjuvant chemotherapy | defined as number of women who get recurrence within two years after conisation | 2 years after conisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fertility | number of patients who are still fertile after treatment | 5 years after treatment | 
| ovarian function | hormone levels will be measured to evaluate ovarian function | 2 years after conisation |