Clinical trial NCT03763123: A Phase 1b Study of Sevacizumab in Combination With Chemotherapy in Chinese Patients With Platinum-Resistant Recurrent Ovarian Cancer.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Ovarian Cancer
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-04
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 3 years
measure: The ratio of adverse of event
timeFrame: 3 years
Secondary outcomes:
measure: Maximum Plasma Concentration [Cmax]
timeFrame: 3 years
measure: Area Under the Curve [AUC],
timeFrame: 3 years
measure: Tmax
timeFrame: 3 years
measure: Objective Response Rate (ORR)
timeFrame: 3 years
measure: Disease Control Rate (DCR)
timeFrame: 3 years
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Progression Free Survival (PFS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: The first affiliated hospital,sun yat-sen university
state: Guangdong
city: Harbin
country: China
facility: the Affiliated Cancer Hospital of Harbin Medical University
state: Hei Longjiang
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hunan
Study officials:
References: