Clinical trial NCT03622827: Postoperative Concurrent Chemoradiotherapy Combined With Endostar for High-risk Early Stage Cervical Cancer
Official title: Postoperative Concurrent Chemoradiotherapy Combined With Recombinant Human Endostatin for High-risk Early Stage Cervical Cancer: A Phase II Pilot Study (ChESS).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Keywords: Adjuvant therapy
chemoradiotherapy
Uterine Cervical Neoplasms
high risk
Endostar
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital of Soochow University
First posted: 2018-08-09
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of postoperative concurrent chemoradiotherapy combined with recombinant human endostatin (Endostar) in patients with high-risk early stage cervical cancer.

Detailed description: This is a pilot phase 2, single arm study to assess the efficacy and safety of concurrent chemoradiotherapy combined with recombinant human endostatin (Endostar) in early stage cervical cancer patients with high risk factor(s).

Postoperative pelvic radiotherapy starts 2-3 weeks after surgery. Intensity modulated radiotherapy (IMRT) is given five fractions per week at 1.8-2 Gy/fraction/day with total prescription dose of 45-50Gy to PTV region. The external beam radiotherapy should be completed within 6 weeks. Concurrent chemotherapy consists of cisplatin (75 mg/m2, day 1-3) and 5-fluorouracil (5-FU; 1000mg/m2/day, civ, day 1-4) for 2 cycles every 3 weeks. Recombinant human endostatin (Endostar,15mg/m2/d, civ, d1-7) is applied 3 days before the concurrent chemoradiotherapy for 2 cycles every 3 weeks.

Aimed to recruit total of 120 cases in this single arm study. The primary endpoint is 3-year disease-free survival and acute toxicity. Secondary endpoints include time to distant metastasis survival, local-regional recurrence free survival, 3 and 5-year overall survival, and safety and tolerability. Quality of life will be evaluated with EORTC-Q30.

Eligibility criteria: Inclusion Criteria:

* Aged between 18 and 70 years.
* Histologically confirmed adenocarcinoma or squamous cervical carcinomas.
* Chest CT scan and ultrasound must be done prior to surgery as to rule out distant metastasis.
* Operable patients with clinical diagnosis of FIGO stage IB-IIA cervical cancer.
* Complete radical hysterectomy of cervical cancer is mandatory. All gross diseases must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor. Para-aortic lymph node sampling is performed according to gynaecologist decision.
* Patients with one of these risk factors:positive pelvic nodes, parametrial invasion, positive surgical margin.OR patients with at least two of following risk factors: tumor size≥4cm,lymphovascular space invasion,stromal invasion≥1/2.
* Performance status 0-2 (ECOG, Eastern Cooperative Oncology Group).
* Adequate organ function is needed, including cardio-respiratory, hepato-renal and hematological reserves: Absolute neutrophil count (ANC)≥1.5×109/L;Platelet count≥100×109/L; ASAT\&ALST\<1.5 times upper limit of normal (ULN) (With hepatic metastases, ASAT\&ALST\<5.0 times upper limit of normal);Bilirubin \<1.5 times ULN;Creatinine≤1.25×ULN or Creatinine clearance≥50 mL/min.
* Signed written informed consent prior to study entry.

Exclusion Criteria:

* Previous radiation or chemotherapy treatment or major pelvic surgery.
* Patients with distant metastasis confirmed by imaging or pathology.
* Other uncured malignant tumors in the past five years, except the cured skin basal cell carcinoma and breast carcinoma in situ.
* Any prior anticancer therapy.
* Unable to tolerate postoperative concurrent chemoradiotherapy.
* Patients with evidence of being allergic to fluorouracil, cisplatin or Endostar.
* Patients with serious comorbidity that might potentially influence the practice of protocol, including severe infection, myocardial infarction, severe arrhythmia, severe cerebrovascular disease, severe mental disorder, etc.
* Patients with Heart related adverse events or thrombotic events in the past 6 months.
* Patients with hepatitis B, hepatitis C and human immunodeficiency virus (HIV) or any other active viral infections.
* Participate in other clinical researchers.
* The estimated survival\<3 months;

Primary outcomes:
measure: 3-year Disease-free survival
timeFrame: 3 years
measure: Acute toxicity
timeFrame: 3 months
Secondary outcomes:
measure: Time to distant metastasis survival
timeFrame: 3 years
measure: Local-regional recurrence free survival
timeFrame: 3 years
measure: 3-year overall survival rate
timeFrame: 3 years
measure: 5-year overall survival rate
timeFrame: 5 years
measure: Quality of Life (QoL)
timeFrame: 3 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The Affiliated Suzhou Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The Affiliated Suzhou Hospital of Nanjing Medical University
name: Ke Gu, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: