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

December 1, 2018 updated by: Jiangsu Simcere Pharmaceutical Co., Ltd.

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.

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
        • Principal Investigator:
          • zheng hong
      • Beijing, Beijing, China
        • Recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences
        • Contact:
        • Principal Investigator:
          • wu lingying
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • The First Affiliated Hospital，Sun Yat-sen University
        • Contact:
        • Contact:
          • Yao Shuzhong
          • Phone Number: 02087755766 02087755766
          • Email: yszlfy@163.com
        • Principal Investigator:
          • Yao Shuzhong
    • Hei Longjiang
      • Harbin, Hei Longjiang, China
        • Suspended
        • The Affiliated Cancer Hospital of Harbin Medical University
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Hunan Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Zhang Keqiang
      • Wuhan, Hunan, China
        • Recruiting
        • Wuhan Union Hospital
        • Contact:
        • Principal Investigator:
          • Li Guiling

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: 3 years
3 years
The ratio of adverse of event
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 3 years
3 years
Overall Survival (OS)
Time Frame: 3 years
3 years
Disease Control Rate (DCR)
Time Frame: 3 years
3 years
Maximum Plasma Concentration [Cmax]
Time Frame: 3 years
Maximum Plasma Concentration [Cmax]
3 years
Area Under the Curve [AUC],
Time Frame: 3 years
Area Under the Curve [AUC]
3 years
Tmax
Time Frame: 3 years
Tmax for Cmax of sevacizumab
3 years
Objective Response Rate (ORR)
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jiangsu Simcere Pharmaceutical Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 24, 2018

Primary Completion (ANTICIPATED)

December 31, 2019

Study Completion (ANTICIPATED)

December 31, 2020

Study Registration Dates

First Submitted

November 25, 2018

First Submitted That Met QC Criteria

December 1, 2018

First Posted (ACTUAL)

December 4, 2018

Study Record Updates

Last Update Posted (ACTUAL)

December 4, 2018

Last Update Submitted That Met QC Criteria

December 1, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SIM-63-OC-101

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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