A Clinical Study of Gimatecan in Advanced Ovarian Epithelial Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer

A Phase I Clinical Study of Gimatecan (ST 1481) in Patients With Platinum-resistant or Sensitive Relapsing/Refractory Advanced Ovarian Epithelial Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer

This is a Phase 1, open-label, dose-escalation ,and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of Gimatecan in Advanced Ovarian Epithelial Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer. To explore the dose-limiting toxicity (DLT) and the maximum tolerable dose (MTD) of oral administration of Gimatecan capsules 5 consecutive days, every 28 days.

Study Overview

• Status: Unknown
• Conditions: Ovarian Epithelial Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: Gimatecan 0.6mg/m2/d; Drug: 0.8mg/m2/d; Drug: 0.4mg/m2/d

Detailed Description

The clinical trial is used the traditional 3 +3 design and conducted in two dose groups, 0.6mg/m2/d and 0.8mg/m2/d, with an improved dose escalation design. The initial dose is 0.6mg/m2, once a day for 5 consecutive days, every 28 days for a course of treatment. Subjects are assigned to the corresponding dose group according to the order of enrolling. DLT is observed within 28 days of the first dose of Gimatecan. In the absence of DLT as prescribed by the protocol, the next dose group is started until the maximum tolerated dose (MTD) is observed.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hong Zheng, MD; Phone Number: 13641356816; Email: Zhhong306@Hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Tumor Hospital
      • Contact: Hong Zheng, MD; Phone Number: 13641356816; Email: Zhhong306@Hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients must have stage III or IV ovarian epithelial cancer, fallopian tube cancer or primary peritoneal cancer.
2. Definite histopathological diagnosis.
3. Failed with treatment for taxane/doxorubicin and platinum.
4. Must have measurable disease with at least 1 unidimensional measurable lesion base on RECIST1.1. When evaluating the efficacy of patients with CA125 level, CA125 abnormalities caused by other reasons should be excluded. According to the Gynecologic Cancer Intergroup-GCIG standard, the baseline serum CA125 level of patients within 2 weeks before treatment should be ≥2 upper limit of normal.
5. Age between 18-65(inclusive).
6. ECOG（Eastern Cooperative Oncology Group） performance status of 0 or 1.
7. To estimated life expectancy of at least 3 months.
8. Appropriate blood routine, liver and kidney function.
9. No allergic history of camptothecin.
10. Patients who are able to take strict contraceptive measures during the trial and within 4 months after the end of the trial.
11. The patients are able to swallow and maintain oral medication.
12. More than 4 weeks from the end of previous surgery, chemotherapy, radiotherapy (non-pelvic and peritoneal sites) and targeted therapy before the study and the body had recovered (the treatment-related toxicity grade is no more than grade 1, except for hair loss and pigmentation).
13. Patients voluntarily give written informed consent to participate in the study.

Exclusion Criteria:

1. The patients are treated with irinotecan or topotecan or with any topoisomerase I inhibitor regimen prior to enrollment.
2. Patients who use other experimental drugs or conducted other clinical trials at the same time within 30 days before participate in the study.
3. To received radiotherapy of pelvic cavity and abdomen.
4. Smoking more than 5 cigarettes per day in the past year.
5. Suspected or real alcohol dependence with an average alcohol intake of more than 2 units per day for 3 months.
6. Active infection.
7. patients with the history of gastrointestinal surgery or that may change drug absorption and activity in the body.
8. Serious cardiovascular disease, including Ⅱ magnitude abnormal cardiac function.
9. having a clear history of neuropathy or mental disorders (including epilepsy or dementia).
10. Human immunodeficiency virus(HIV) positive, untreated active hepatitis.
11. Suffering from other malignant tumors other than this diseases in 5 years, except for basal cell carcinoma of skin, skin squamous cell carcinoma, primary cervical carcinoma and breast cancer without recurrence and metastasis after radical operation.
12. Brain metastasis.
13. Female with pregnant or lactating.
14. Patients who are considered unsuitable to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gimatecan 0.6mg/m2/d; Three or six patients will be treated with the dose of 0.6mg/m2/d for once a day for 5 consecutive days of Gimatecan. DLT will be observed within 28 days after administration.	Drug: Gimatecan 0.6mg/m2/d; 0.6mg/m2/d for once a day for 5 consecutive days of Gimatecan
Experimental: Gimatecan 0.8mg/m2/d; Three or six patients will be treated with the dose of 0.8mg/m2/d for once a day for 5 consecutive days of Gimatecan. DLT will be observed within 28 days after administration.	Drug: 0.8mg/m2/d; 0.8mg/m2/d for once a day for 5 consecutive days of Gimatecan
Experimental: Gimatecan 0.4mg/m2/d; Three or six patients will be treated with the dose of 0.4mg/m2/d for once a day for 5 consecutive days of Gimatecan. DLT will be observed within 28 days after administration.	Drug: 0.4mg/m2/d; 0.4mg/m2/d for once a day for 5 consecutive days of Gimatecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity(DLT)	Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v5.0.	28 days after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal tolerable dose(MTD)	DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.	28 days after first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate(ORR)	The proportion of subjects who achieve the optimal objective response rate(PR or CR).	through study completion, an average of 2 years
AUC(0-t)	Area under curve 0-t	28 days after first dose
Cmax	Peak concentration	28 days after first dose
Tmax	Peak concentration	28 days after first dose
T1/2	Half life	28 days after first dose

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited
• Investigators: Study Director: Hong Zheng, MD, Beijing Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 21, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 21, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: NTL-LEES-2018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No