1.Primary purpose: Belotecan in patients with recurrent or persistent cervical cancer
response rate by RECIST by conducting a phase 2 study administered single-dose
(Response Rate, RR,%) and evaluate anticancer effect.
2. Secondary Purpose:
1) Check Progression free survival.
2) Check safety by checking for toxicity (adverse reactions)

Background >
Cervical cancer is the second leading cause of cancer deaths worldwide, with 510,000 new cases reported each year and 280,000 deaths reported each year. The incidence of cervical cancer has decreased significantly since the introduction of screening tests such as cervical cytology and HPV, but overall mortality has not changed much compared to the past. In particular, the prognosis for advanced cervical cancer, recurrent or persistent cervical cancer is very poor. The 5-year survival rate for locally advanced stage cervical cancer is 41-51%, whereas recurrent or persistent cervical cancer responds very poorly to current methods of treatment, with a 5-year survival rate of only 8-17%. belotecan is a novel camptothecin derivative that inhibits topoisomerase I activity and has shown good antitumor response in a phase 1 study of solid cancer. belotecan preclinical studies showed a wide range of antitumor responses in various human tumor cell lines and similar or better antitumor responses compared to topotecan. In recent years of resistant and recurrent ovarian cancer studies, belotecan has shown acceptable toxicity and excellent anti-tumor responses.
 However, in a phase 2 study administered with belotecan alone, there was no complete or partial response in all 16 patients with resistant recurrent cervical cancer, and overall survival was only 12.38 months. The reason for the lower response rate in this study than other studies using topotecan was attributed to patient selection. In the previous Topotecan study, patients were either never treated with chemotherapy or had been treated with a single chemotherapy. The antitumor response of belotecans would have been low. Related studies in which topotecan was administered monotherapy were as follows. Topotecan has been shown to be effective in colon cancer, breast cancer, ovarian cancer, kidney cancer, non-small cell lung cancer and gastrointestinal cancer in preclinical and animal studies. In Phase 1 clinical trials by Rowinsky et al, complete response, partial response in various solid cancer patients, and myelosuppression was the most common dose-limiting toxicity.

In a GOG 76-U study conducted by Muderspach et al., A 1.5 mg / m2 intravenous injection every five weeks was performed for patients with advanced, recurrent, or persistent cervical squamous cell carcinoma who had not previously received chemotherapy. The mean disease-free survival rate was 2.4 months and the average overall survival rate was 6.4 months. The overall response rate (complete + partial) was 18.6%. In the GOG 127-F study, three-week intervals and five days were administered to patients with cervical cancer who had previously received chemotherapy in the multicenter phase II study. The overall response rate was 12.5%, disease free survival rate 2.1 months, and overall survival rate 6.6 months. . Considering the fact that Topoisomerase I inhibitors show significant anti-tumor reactions in cervical cancer alone or in combination therapy, belotecan are expected to show notable responses in cervical cancer.

In this study, we evaluated the rate of response in patients with recurrent or persistent cervical cancer by administering belotecan alone.

Treatment

Belotecan 0.5mg/m2 IV on day 1-5, Every 3weeks, 6cycles

Arm Label

Target Number of Participant

Arm Type

Arm Description

Belotecan 0.5mg/m2 IV on day 1-5, Every 3weeks, 6cycles

Gender

Age

Description

1) over 19 years old
2) Recurrence after surgery or concurrent chemoradiotherapy for initial treatment as a persistent cervical cancer patient, 
 3) histologically squamous cell carcinoma
4) RECIST standard version 1.1 (standard for evaluation of response in solid cancer)
Abnormally measurable lesions (one-dimensional measurable lesions)
5) Patients with normal haematological functions, kidney and liver functions, at least the following long-term functions shall be measured;The target shall measure the normal organs and marrow functions defined below within 7 days before starting the treatment.
Defined organs Organ and bone marrow function was measured.
Hemoglobin ≥10 g / dL
Absolute neutrophil count (ANC)> ≥ 1.5x10P9P / L
Platelets ≥ 100x 10P9P / L
-AST / ALT ≤ 3 x ULN, if transition to liver ≤ 5 x ULN
Creatinine ≤ ULN or calculated CrCl ≥ 50ml / min
6) Patients with an expected survival period of 3 months or more
7) ECOG 0-2

1) Histologically neuroendocrine type
2) Two or more regimens previously with recurrent / persistent cervical cancer If you received chemotherapy
3) If you have previously received topoisomerase I inhibitor
4) When bilateral receipt is not resolved by ureteral stent or percutaneous drainage
5) In case of brain metastasis
6) Non-melanoma skin cancer is accompanied by cancer diseases
7) If you have been previously treated for invasive cancer (except Non-melanoma skin cancer)
8) received systemic chemotherapy or radiation therapy within 3 weeks prior to clinical trial administration Patients (excluding radiation therapy for palliative care purposes)

Analyze the complete response rate through CT or MRI or PET imaging tests

every 3cycle

Progression-free survival : Analyze survival outcomes using the Kaplan-Meir method

every 3cycle

Side-effect

every cycle