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.

Jiangsu Simcere Pharmaceutical Co., Ltd.6 sites in 1 country48 target enrollmentApril 24, 2018

Overview

Brief 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).

Detailed 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).

Registry

clinicaltrials.gov

Start Date

April 24, 2018

End Date

December 31, 2020

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Jiangsu Simcere Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•age≥18 years
•Histologically documented platinum resistant
•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.
•At least one measurable leision. (according to RECIST 1.1 )
•Eastern Cooperative Oncology Group performance status (ECOG PS) 0-
•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
•Progression within 6 months from completion of a minimum of 4 platinum therapy cycles.
•Life expectancy ≥12 weeks.
•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
•Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)

Exclusion Criteria

•Previous treatment with \> 2 anti-cancer regimens.
•Patients whose disease was refractory to their previous platinum treatment. (Refractory disease was defined as those patients who progressed during the preceding platinum treatment.)
•Ovarian tumors with low malignant potential (i.e. borderline tumors).
•Patients with a prior invasive malignancy (except non-melanoma skin cancer) or whose prior malignancy treatment contraindicated the current protocol therapy.
•Any prior radiotherapy to the pelvis or abdomen.
•Patients with serious non-healing wound, ulcer, or bone fracture.
•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.
•Serious infection requiring intravenous antibiotic therapy
•history or evidence of thrombotic or hemorrhagic disorder within 6 months before first study treatment
•untreated CNS disease unrelated to cancer or symptomatic CNS metastasis

Arms & Interventions

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Investigators selected single-agent chemotherapy on an individual patient basis from the following options, with appropriate premedication according to local standards: paclitaxel 80mg/m2 intravenously (IV)on days 1, 8, 15, and 22 every 4 weeks; or topotecan 4 mg/m2 IV on days 1, 8, and 15 every 4 weeks.

Intervention: Sevacizumab

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Investigators selected single-agent chemotherapy on an individual patient basis from the following options, with appropriate premedication according to local standards: paclitaxel 80mg/m2 intravenously (IV)on days 1, 8, 15, and 22 every 4 weeks; or topotecan 4 mg/m2 IV on days 1, 8, and 15 every 4 weeks.

Intervention: Paclitaxel

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Investigators selected single-agent chemotherapy on an individual patient basis from the following options, with appropriate premedication according to local standards: paclitaxel 80mg/m2 intravenously (IV)on days 1, 8, 15, and 22 every 4 weeks; or topotecan 4 mg/m2 IV on days 1, 8, and 15 every 4 weeks.

Intervention: Topotecan