A Study on the Efficacy and Safety of Bevacizumab in Untreated Patients With Locally Advanced Cervical Cancer

NCT ID: NCT04138992

Last Updated: 2020-06-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-01
• Study Completion Date: 2022-05-31

Brief Summary

To verify the clinical efficacy and safety of bevacizumab in treating local advanced cervical cancer, present study was designed to investigate the clinical results of bevacizumab combined with concurrent chemoradiotherapy (CCRT) in local advanced cervical cancer

Detailed Description

Cervical cancer is the most common malignant tumor of the female productive system in developing countries and regions. Since five large-sample randomized controlled clinical trials have reported that concurrent chemoradiotherapy can improve the survival rate of patients with cervical cancer in the early 20th century, cisplatin-based concurrent chemoradiotherapy has become the standard treatment for locally advanced cervical cancer (LACC) . LACC has the characteristics of high invasiveness, high lymphatic metastasis and poor prognosis. The size and stage of the tumor are two independent prognostic factors. In 2008, a retrospective study published in Journal of Clinical Oncology(JCO) suggested that single-agent concurrent chemoradiotherapy did not improve disease-free survival (DFS) or overall survival (OS) for patients with FIGO stage II-IVA tumors. Multiple studies reported poor prognosis in patients with primary tumors whose diameters were larger than 4 cm, 5 cm or 6 cm , and in 2016, Fokdal. et al. reported a low local control rate if the residual tumor volume was larger than 30 cc prior to afterloading brachytherapy . In the EMBRACE trial, Jastaniyah et al. divided tumors into five groups based on the difference between the tumor volume before treatment and prior to afterloading brachytherapy, and found that the dose coverage of the HR-CTV by D90 was low for patients with a large primary tumor volume and a poor treatment response [13]. Therefore, for patients with a large primary tumor volume, further studies are required to investigate whether accelerated tumor volume regression prior to afterloading brachytherapy is meaningful to escalating the local afterloading dose delivered to tumor and improving the local control rate and OS.

In recent years, with the rapid development of molecular biology, there have been multiple clinical trials regarding the molecular targeted drug therapy for tumor cell-specific targets . The angiogenesis inhibitor, bevacizumab, is the first molecular targeted drug for recurrent or advanced cervical cancer, which inhibits tumor angiogenesis by blocking the function of the vascular endothelial growth factor (VEGF). In a GOG phase II clinical trial, bevacizumab was applied to 46 patients with recurrent cervical cancer. The study reported a progression-free survival (PFS) of more than 6 months, with a median PFS and a median OS of 3.50 months and 7.29 months, respectively. Another GOG240 phase III clinical trial showed that chemotherapy combined with bevacizumab extended the OS of patients with recurrent and metastatic cervical cancer. United States' NCCN Clinical Practice Guidelines recommend the combined use of bevacizumab with paclitaxel + cisplatin for the first-line treatment of current and metastatic cervical cancer. However, there is a lack of evidence for the use of bevacizumab in the treatment of LACC.

The above background information raises the questions of: during the initial treatment of LACC, can the introduction of bevacizumab improve the patient's tumor regression rate and OS? And compared to concurrent chemoradiotherapy directly combined with bevacizumab, can neoadjuvant chemotherapy combined with bevacizumab + concurrent chemoradiotherapy further improve the therapeutic outcome? However, currently there is no research on these topics. In 2017, our research team reported poor prognosis in patients with LACC who had a high VEGFR expression . This result indicated that anti-angiogenic therapy could benefit patients with LACC. To investigate the clinical efficacy and safety of bevacizumab in treating local advanced cervical cancer, we design this clinical study

Conditions

Disease Free Survival

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study group A

bevacizumab combined with neoadjuvant chemotherapy and concurrent chemoradiotherapy：

1. bevacizumab combined with neoadjuvant chemotherapy for 2 cycles: Bevacizumab will be used as 7.5 mg/kg, once every three weeks; DDP 75mg/m2, intravenous injection，once three week; Docetaxel 75mg/m2, intravenous injection，once three week;

2. bevacizumab combined with concurrent chemoradiotherapy: Bevacizumab will be used as 7.5 mg/kg, once every three weeks; DDP 75mg/m2, intravenous injection，once three week pelvic radiotherapy will be delivered with 45-50Gy/25f; enlarged lymph nodes be irradiated by 62.5Gy/25f with sib-IMRT; brachytherapy be delivered to cervix and primary tumor

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: DRUG

bevacizumab will be used during neoadjuvant and concurrent chemoradiotherapy

DDP

Intervention Type: DRUG

DDP will be used during neoadjuvant and concurrent chemoradiotherapy

Docetaxel

Intervention Type: DRUG

used in neoadjuvant chemotherapy

radiotherapy

Intervention Type: RADIATION

standard treatment includes pelvic external beam radiation and brachytherapy

study group B

study arm: bevacizumab combined with concurrent chemoradiotherapy： Bevacizumab will be used as 7.5 mg/kg, once every three weeks; DDP 75mg/m2, intravenous injection，once three week; pelvic radiotherapy will be delivered with 45-50Gy/25f; enlarged lymph nodes be irradiated by 62.5Gy/25f with sib-IMRT; brachytherapy be delivered to cervix and primary tumor

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: DRUG

bevacizumab will be used during neoadjuvant and concurrent chemoradiotherapy

DDP

Intervention Type: DRUG

DDP will be used during neoadjuvant and concurrent chemoradiotherapy

radiotherapy

Intervention Type: RADIATION

standard treatment includes pelvic external beam radiation and brachytherapy

control

standard concurrent chemoradiotherapy: DDP 40mg/m2, intravenous injection，once a week; pelvic radiotherapy will be delivered with 45-50Gy/25f; enlarged lymph nodes be irradiated by 62.5Gy/25f with sib-IMRT; brachytherapy be delivered to cervix and primary tumor

Group Type: ACTIVE_COMPARATOR

DDP

Intervention Type: DRUG

DDP will be used during neoadjuvant and concurrent chemoradiotherapy

radiotherapy

Intervention Type: RADIATION

standard treatment includes pelvic external beam radiation and brachytherapy

Interventions

bevacizumab

bevacizumab will be used during neoadjuvant and concurrent chemoradiotherapy

Intervention Type: DRUG

DDP

DDP will be used during neoadjuvant and concurrent chemoradiotherapy

Intervention Type: DRUG

Docetaxel

used in neoadjuvant chemotherapy

Intervention Type: DRUG

radiotherapy

standard treatment includes pelvic external beam radiation and brachytherapy

Intervention Type: RADIATION

Other Intervention Names

Avastin; Cisplatin; RT

Eligibility Criteria

Inclusion Criteria

1. Biopsy-proven, invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix

2. 2018FIGO clinical stage I-IIIC disease

Exclusion Criteria

1， Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; 2， Prior systemic chemotherapy within the past three years; 3， Prior radiotherapy to the pelvis or abdomen ; 4， Distant metastasis; 5， Severe, active co-morbidity; 6， patients with FIGO stage IVA 7， Bevacizumab is prohibited to the patients with active bleeding and hypertension

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Air Force Military Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Mei Shi

head of department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

mei shi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Xijing Hospital

Locations

Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lichun Wei, physician

Role: CONTACT

weilichun@fmmu.edu.cn

029-84775432

ying zhang, physician

Role: CONTACT

zhangying@fmmu.edu.cn

029-84775432

Facility Contacts

Lichun Wei, MD

Role: primary

weilichun@fmmu.edu.cn

+86-029-84775425

Related Links

http://ncbi.nlm.nih.gov

Bevacizumab

Other Identifiers

XJFL-2019-01-LACC-bevacizumab

Identifier Type: -

Identifier Source: org_study_id