A Phase 1b Study of Sevacizumab in Combination With Chemotherapy in Chinese Patients With Platinum-Resistant Recurrent Ovarian Cancer.

Ovarian Cancer Clinical Trial

Official title:

A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus Chemotherapy in Chinese Patients With Platinum-Resistant Recurrent Ovarian Cancer.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03763123
• Other study ID #: SIM-63-OC-101
• Status: Recruiting
• Phase: Phase 1
• Start date: April 24, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2018
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).

Description:

This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. age=18 years

2. Histologically documented platinum resistant

3. EOC, FTC, or PPC of the following types: adenocarcinoma not otherwise specified (NOS), clear cell adenocarcinoma, endometriod adenocarcinoma, malignant Brenner's tumor, mixed epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell carcinoma and undifferentiated carcinoma.

4. At least one measurable leision. (according to RECIST 1.1 )

5. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.

6. Adequate hematologic function: ANC = 1.5 × 10^9 /L, HB = 90 g /L (blood transfusion allowed), PLT = 100 ×10^9 /L; Adequate hepatic function: ALT = 2.5 × ULN, AST = 2.5 × ULN, TBIL = 1.5 × ULN (patients with liver metastases ALT = 5 × ULN, AST = 5 × ULN); Adequate renal function: creatinine = 1 × ULN; Coagulation function: INR = 1.5 × ULN, APTT = 1.5 × ULN

7. Progression within 6 months from completion of a minimum of 4 platinum therapy cycles.

8. Life expectancy =12 weeks.

9. At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed

10. Toxicity from previous treatment has to restore to = grade 1 (NCI CTC4.0)

11. Patients signed written inform consent.

12. Willingness and capability to communicate with investigators and to comply with protocol requirements

Exclusion Criteria:

1. Previous treatment with > 2 anti-cancer regimens.

2. Patients whose disease was refractory to their previous platinum treatment. (Refractory disease was defined as those patients who progressed during the preceding platinum treatment.)

3. Ovarian tumors with low malignant potential (i.e. borderline tumors).

4. Patients with a prior invasive malignancy (except non-melanoma skin cancer) or whose prior malignancy treatment contraindicated the current protocol therapy.

5. Any prior radiotherapy to the pelvis or abdomen.

6. Patients with serious non-healing wound, ulcer, or bone fracture.

7. patients with a history of bowel obstruction (including subocclusive disease) related to underlying disease, a history of abdominal fistula, GI perforation, or intra-abdominal abscess or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on computed tomography, or clinical symptoms of bowel obstruction.

8. Serious infection requiring intravenous antibiotic therapy

9. history or evidence of thrombotic or hemorrhagic disorder within 6 months before first study treatment

10. untreated CNS disease unrelated to cancer or symptomatic CNS metastasis

11. Patients with clinically significant cardiovascular disease. This included:Uncontrolled hypertension, defined as systolic > 150 mmHg or diastolic > 90 mmHg;Myocardial infarction or unstable angina > 6 months prior to registration;New York Heart Association (NYHA) Grade II or greater congestive heart failure;Serious cardiac arrhythmia requiring medication. This did not include asymptomatic, atrial fibrillation with controlled ventricular rate.

12. left ventricular ejection fraction below the institutional lower limit of normal

13. pre-existing neuropathy = CTC Grade 2 for those in the paclitaxel group

14. Known allergies to any excipient in the study drug

15. Pregnant and lactating women

16. Patients with proteinuria (urine protein >1+ at screening, or urine protein 1+, not recover to normal value within 24h)

17. Previously received anti-VEGF protein drugs, such as Bevacizumab, Sevacizumab

18. Patients with or with anticipation of invasive procedures as defined below:Major surgical procedure or significant traumatic injury within 28 days prior to the first date of sevacizumab therapy;Major surgical procedure anticipated during the course of the study. This included, but was not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression;Core biopsy, within 7 days prior to randomization.

19. Participation in other clinical trials within 4 weeks before enrollment

20. The investigators consider the patients are not suitable for this trial.

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Sevacizumab
Drug: Sevacizumab escalating doses of Sevacizumab : 0.5mg/kg,1mg/kg,1.5mg/kg and 2mg/kg
• Paclitaxel
paclitaxel 80mg/m2 as a > 3-hour IV infusion on days 1, 8,15, and 22 every 4 weeks;
• Topotecan
topotecan 4 mg/m2 as a >30 minute IV infusion on days 1, 8, and 15 every 4 weeks ;

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	The first affiliated hospital,sun yat-sen university	Guangzhou	Guangdong
China	the Affiliated Cancer Hospital of Harbin Medical University	Harbin	Hei Longjiang
China	Wuhan Union Hospital	Wuhan	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		3 years
Primary	The ratio of adverse of event		3 years
Secondary	Maximum Plasma Concentration [Cmax]	Maximum Plasma Concentration [Cmax]	3 years
Secondary	Area Under the Curve [AUC],	Area Under the Curve [AUC]	3 years
Secondary	Tmax	Tmax for Cmax of sevacizumab	3 years
Secondary	Objective Response Rate (ORR)		3 years
Secondary	Disease Control Rate (DCR)		3 years
Secondary	Overall Survival (OS)		3 years
Secondary	Progression Free Survival (PFS)		3 years