Randomized Control Trial on Efficacy and Safety of Concurrent and Adjuvant Chemotherapy for the Cervical Cancer

Phase 3

• Conditions: Cervical Cancer
• Interventions: Drug: concurrent chemotherapy with cisplatin; Drug: concurrent chemotherapy with docetaxel; Radiation: pelvic radiotherapy; Radiation: brachytherapy; Drug: adjuvant chemotherapy with cisplatin and docetaxel

• Registration Number: NCT02703961
• Lead Sponsor: Air Force Military Medical University, China

Brief Summary

The standard treatment of local advanced cervical cancer is concurrent chemoradiotherapy. The 3 year disease free survival was about 50-70%. The distant metastasis is the main cause of failure in local advanced cervical cancer treated with 3-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiotherapy (IMRT). The purpose of this study is to investigate the efficacy and tolerance of concurrent and adjuvant chemotherapy with cisplatin and docetaxel for local advanced cervical cancer. It was expected that the 3 year disease free survival would be increased by 10% with this new treatment schedule.

Detailed Description

The cervical cancer is the most common malignant gynecological tumor in the developing area. From 1999, the concurrent chemoradiotherapy has been established as the standard treatment for local advanced cervical cancer. The modern radiotherapy techniques, such as 3 dimensional conformal radiotherapy(3D-CRT), intensity modulated radiotherapy(IMRT), image guided 3-dimensional brachytherapy(3D-BT), was widely used for the treatment of cervical cancer. The recently clinical outcome showed that the 3 year local and regional control was more than 90%［1-3］. The distant metastasis has proved to be the main cause of failure and death, especially for the patient with pelvic lymph node metastasis, large volume of tumor and advanced FIGO stage. the data showed that the 3 year distant metastasis free survival and overall survival were 64.7% and 64.6% respectively for the patient with huge pelvic lymph node metastasis and FIGO stage III- IVA. The system treatment pointing at the distant metastasis has become to be the topic of clinical investigation.

Dueñas-González A'［4］ study demonstrated that the 3 year progress free survival and distant metastasis free survival has increased by 8.9% and 8.3% by the radial radiotherapy combined with concurrent chemotherapy with weekly gemcitabine and cisplatin and adjuvant chemotherapy with triweekly gemcitabine and cisplatin. Ryu SY［5］ also reported the triweekly concurrent cisplatin with 3 cycles improved survival outcomes compared with weekly concurrent cisplatin. Retrospective studies by Tang and Jelavić-TB［6-7］ suggested that the adjubant chemotherapy after CCRT has better DMFS and OS.

The aim of present study is to prospectively investigate the efficacy and safety of concurrent and adjuvant chemotherapy with cisplatin and docetaxel for patients with local advanced cervical cancer, especially for those with FIGO III-IVA with or without pelvic lymph node metastasis and the FIGO IB2-IIB with pelvic lymph node metastasis.

Study Timeline

• Study Start: 2016-02
• Status Verified: 2016-03
• Study First Submitted: 2016-03-03
• Study First Submitted QC: 2016-03-04
• Study First Posted: 2016-03-09
• Last Update Submitted: 2016-03-15
• Last Update Posted: 2016-03-17
• Primary Completion: 2018-02
• Study Completion: 2021-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 598

Inclusion Criteria

1. Biopsy-proven, invasive squamous cell carcinoma, adenocarcinoma, or adenosquamouscarcinoma of the cervix
2. FIGO clinical stage IB2-IIB with pelvic lymph node metastasis or FIGO clinical stage III-IVA with or without pelvic lymph node metastasis
3. ECOG performance score 0-1
4. The bone marrow, hepatic and renal function was normal at registration
5. The patients signed informed consent

Exclusion Criteria

1. clear cell and small cell neuroendocrine, sarcoma
2. FIGO stage IVB
3. Prior invasive malignancy
4. Prior systemic chemotherapy
5. Prior radiotherapy to the pelvis or abdomen
6. Severe, active co-morbidity
7. Women who are pregnant
8. immunocompromised status

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
experimental	concurrent chemotherapy with cisplatin	concurrent and adjuvant chemotherapy with cisplatin and docetaxel combined radical radiotherapy. During external beam radiotherapy: cisplatin 60mg/m2, d1,d22; docetaxel 60mg/m2, d1,d22. After external beam radiotherapy: cisplatin 75mg/m2, d43,d64; The patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy. docetaxel 75mg/m2, d43,d64.
experimental	pelvic radiotherapy	concurrent and adjuvant chemotherapy with cisplatin and docetaxel combined radical radiotherapy. During external beam radiotherapy: cisplatin 60mg/m2, d1,d22; docetaxel 60mg/m2, d1,d22. After external beam radiotherapy: cisplatin 75mg/m2, d43,d64; The patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy. docetaxel 75mg/m2, d43,d64.
experimental	brachytherapy	concurrent and adjuvant chemotherapy with cisplatin and docetaxel combined radical radiotherapy. During external beam radiotherapy: cisplatin 60mg/m2, d1,d22; docetaxel 60mg/m2, d1,d22. After external beam radiotherapy: cisplatin 75mg/m2, d43,d64; The patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy. docetaxel 75mg/m2, d43,d64.
control	concurrent chemotherapy with cisplatin	standard chemoradiotherapy with weekly cisplatin. Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy.
control	pelvic radiotherapy	standard chemoradiotherapy with weekly cisplatin. Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy.
control	brachytherapy	standard chemoradiotherapy with weekly cisplatin. Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy.
experimental	concurrent chemotherapy with docetaxel	concurrent and adjuvant chemotherapy with cisplatin and docetaxel combined radical radiotherapy. During external beam radiotherapy: cisplatin 60mg/m2, d1,d22; docetaxel 60mg/m2, d1,d22. After external beam radiotherapy: cisplatin 75mg/m2, d43,d64; The patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy. docetaxel 75mg/m2, d43,d64.
experimental	adjuvant chemotherapy with cisplatin and docetaxel	concurrent and adjuvant chemotherapy with cisplatin and docetaxel combined radical radiotherapy. During external beam radiotherapy: cisplatin 60mg/m2, d1,d22; docetaxel 60mg/m2, d1,d22. After external beam radiotherapy: cisplatin 75mg/m2, d43,d64; The patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate intracavitary brachytherapy. docetaxel 75mg/m2, d43,d64.

Primary Outcome Measures

Name	Time	Method
disease free survival	3 year

Secondary Outcome Measures

Name	Time	Method
overall survival	3 year

Trial Locations

Locations (3)

Xijing hospital, the Fourth Military Medical University; 🇨🇳 Xi' An, Shaanxi, China

Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 🇨🇳 Xi'an, Shanxi, China

Department of Radiation Oncology, Xijing Hospital, Fourth Military; 🇨🇳 Xi'an, Shanxi, China