Clinical trial NCT01847118: A Phase Ia, Dose Escalation Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in Patients With Advanced or Metastatic Solid Tumors
Official title: A Phase Ia, Dose Escalation Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Metastatic Solid Tumors
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-05-06
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to assess the safety, tolerability and pharmacokinetics of single dose and multiple doses of humanized anti-VEGF monoclonal antibody (Sevacizumab) in patients with advanced or metastatic solid tumors. The secondary objective is to explore the preliminary anti-tumor effects.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced or metastatic malignant solid tumors;
* Patients failed the standard anti-tumor therapy or don't have standard regimen;
* At least one measurable lesion;
* At least 4 weeks from the last chemotherapy, 6 weeks from mitomycin, and nitrosourea treatment. 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);
* ECOG performance status 0-1;
* Life expectancy ≥ 3 months;
* 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, TBIL ≤ 3 × ULN);
* Adequate renal function: creatinine ≤ 1 × ULN;
* Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN;
* Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose.

Exclusion Criteria:

* HCV, TP or HIV antibody positive;
* Previously received anti-VEGF protein drugs, such as bevacizumab;
* Histologically proven squamous cell lung cancer or squamous cell carcinoma of the head and neck;
* Active hepatitis B infection;
* Evidence of serious infection;
* Symptomatic brain metastases;
* Patients with proteinuria at screening (urine protein ≥ 1+);
* History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment;
* Serious non-healing wounds, ulcers or fractures;
* Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment;
* Active bleeding within 3 months prior to enrollment;
* Bleeding diathesis or coagulation disorder;
* History of arterial or venous thrombosis;
* History of myocardial infarction or stroke within 6 months prior to enrollment;
* Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension (systolic blood pressure\> 150 mmHg and/or diastolic blood pressure\> 100 mmHg);
* Pregnant and lactating women;
* Known allergies to any excipient in the study drug;
* Patients with alcohol or drug dependence;
* Participation in other clinical trials within 4 weeks before enrollment.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to 28 days
Secondary outcomes:
measure: Cmax
timeFrame: d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
measure: tmax
timeFrame: d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
measure: AUC
timeFrame: d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
measure: t1/2
timeFrame: d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
measure: Objective Response Rate (ORR)
timeFrame: d29, d86
measure: Disease Control Rate (DCR)
timeFrame: d29, d86
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Jin Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: