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.
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 48
- Locations
- 6
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study 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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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)
- •Patients signed written inform consent.
- •Willingness and capability to communicate with investigators and to comply with protocol requirements
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
- •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
- •Patients with proteinuria (urine protein >1+ at screening, or urine protein 1+, not recover to normal value within 24h)
- •Previously received anti-VEGF protein drugs, such as Bevacizumab, Sevacizumab
- •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.
- •Participation in other clinical trials within 4 weeks before enrollment
- •The investigators consider the patients are not suitable for this trial.
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 (Drug)
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 (Drug)
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 (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: 3 years
The ratio of adverse of event
Time Frame: 3 years
Secondary Outcomes
- Area Under the Curve [AUC],(3 years)
- Tmax(3 years)
- Maximum Plasma Concentration [Cmax](3 years)
- Objective Response Rate (ORR)(3 years)
- Disease Control Rate (DCR)(3 years)
- Overall Survival (OS)(3 years)
- Progression Free Survival (PFS)(3 years)