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

NCT03763123 | Unknown Phase 1

• 1 other identifier: SIM-63-OC-101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

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).

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  3 years

• The ratio of adverse of event

  3 years

Secondary Outcomes (7)

• Maximum Plasma Concentration [Cmax]

  3 years

• Area Under the Curve [AUC],

  3 years

• Tmax

  3 years

• Objective Response Rate (ORR)

  3 years

• Disease Control Rate (DCR)

  3 years

Study Arms (1)

Sevacizumab +Chemotherapy Combined chemotherapy drug including

EXPERIMENTAL

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: Paclitaxel; Drug: Topotecan

Interventions

Sevacizumab DRUG

Drug: Sevacizumab escalating doses of Sevacizumab : 0.5mg/kg，1mg/kg，1.5mg/kg and 2mg/kg

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Paclitaxel DRUG

paclitaxel 80mg/m2 as a \> 3-hour IV infusion on days 1, 8,15, and 22 every 4 weeks;

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Topotecan DRUG

topotecan 4 mg/m2 as a \>30 minute IV infusion on days 1, 8, and 15 every 4 weeks ;

Sevacizumab +Chemotherapy Combined chemotherapy drug including

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) 0-1.
• 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)
• Patients signed written inform consent.
• Willingness and capability to communicate with investigators and to comply with protocol requirements

You may not qualify if:

• 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
• 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.
• left ventricular ejection fraction below the institutional lower limit of normal
• pre-existing neuropathy ≥ CTC Grade 2 for those in the paclitaxel group
• Known allergies to any excipient in the study drug
• Pregnant and lactating women

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (6)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

RECRUITING

The first affiliated hospital,sun yat-sen university

Guangzhou, Guangdong, China

RECRUITING

the Affiliated Cancer Hospital of Harbin Medical University

Harbin, Hei Longjiang, China

SUSPENDED

Hunan Cancer Hospital

Changsha, Hunan, China

RECRUITING

Wuhan Union Hospital

Wuhan, Hunan, China

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Paclitaxel; Topotecan

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2018
• First Posted: December 4, 2018
• Study Start: April 24, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2020
• Last Updated: December 4, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)