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

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ClinicalTrials.gov Identifier: NCT03763123
Recruitment Status : Recruiting
First Posted : December 4, 2018
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Jiangsu Simcere Pharmaceutical Co., Ltd.

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).

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Sevacizumab Drug: Paclitaxel Drug: Topotecan Phase 1

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
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2020


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 ;




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 3 years ]
  2. The ratio of adverse of event [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Maximum Plasma Concentration [Cmax] [ Time Frame: 3 years ]
    Maximum Plasma Concentration [Cmax]

  2. Area Under the Curve [AUC], [ Time Frame: 3 years ]
    Area Under the Curve [AUC]

  3. Tmax [ Time Frame: 3 years ]
    Tmax for Cmax of sevacizumab

  4. Objective Response Rate (ORR) [ Time Frame: 3 years ]
  5. Disease Control Rate (DCR) [ Time Frame: 3 years ]
  6. Overall Survival (OS) [ Time Frame: 3 years ]
  7. Progression Free Survival (PFS) [ Time Frame: 3 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03763123


Locations
China, Beijing
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China
Contact: zheng hong    010-88196102    zhhong306@hotmail.com   
Principal Investigator: zheng hong         
Cancer Hospital Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China
Contact: Wu Lingying    010-87788787    wulingying@csco.org.cn   
Principal Investigator: wu lingying         
China, Guangdong
The first affiliated hospital,sun yat-sen university Recruiting
Guangzhou, Guangdong, China
Contact: Yao Shuzhong    020-87755766 ext 8185    yszlfy@163.com   
Contact: Yao Shuzhong    02087755766 ext 02087755766    yszlfy@163.com   
Principal Investigator: Yao Shuzhong         
China, Hei Longjiang
the Affiliated Cancer Hospital of Harbin Medical University Suspended
Harbin, Hei Longjiang, China
China, Hunan
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China
Contact: Zhang Keqiang    0731-89762695 ext 073189762695    1465217100@qq.com   
Contact: Zhang Keqiang    073189762695 ext 073189762695    1465217100@qq.com   
Principal Investigator: Zhang Keqiang         
Wuhan Union Hospital Recruiting
Wuhan, Hunan, China
Contact: Li Guiling    027-83691785    lgl6714@163.com   
Principal Investigator: Li Guiling         
Sponsors and Collaborators
Jiangsu Simcere Pharmaceutical Co., Ltd.

Responsible Party: Jiangsu Simcere Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT03763123     History of Changes
Other Study ID Numbers: SIM-63-OC-101
First Posted: December 4, 2018    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Paclitaxel
Albumin-Bound Paclitaxel
Topotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors