A phase 2 study of GX-I7 in combination with bevacizumab in recurrent glioblastoma (GBM) patients
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 20
1)Subjects (or a legally acceptable representative, if applicable) must be willing and able to provide written informed consent/assent for the trial.
2)Age = 19 years
3)Histologically diagnosed glioblastoma patients who have been confirmed the progression of disease after attempting standard therapy (RT/CCRT and/or adjuvant chemotherapy (TMZ)),
a.For subjects who have had surgery after recurrence, residual and measurable lesions after surgery are not required, but surgery must have confirmed the recurrence, and the post-surgery MRI should be available within 48 hours of surgery. Screening is possible at least 2 weeks after surgery and subjects must be fully recovered from surgery. The administration of investigational product is possible after 28 days of the last surgery (a major surgery requiring general anesthesia, including biopsy and surgical resection)
b.For subjects who did not operate after recurrence, the recurrent disease should be at least one-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan with minimum diameters of 100 mm, visible on 2 or more axial slices 5 mm apart, based on MRI scan measured within 2 weeks before the enrollment
4)Karnofsky Performance Status; KPS = 60
5)Life expectancy > 12 weeks
6)Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the screening period
a.Absolute neutrophil count (ANC) = 1,500 cells/µL
b.Hemoglobin = 9 g/dL
c.Platelet count = 100,000/µL
d.Total bilirubin = 1.5 × the upper limit of normal (ULN)
e.AST and ALT = 2.5 × ULN
f.Alkaline phosphatase = 2.5 × ULN
g.Serum creatinine = 1.5 × ULN
h.Urine dipstick for proteinuria <2+
7)Subjects on corticosteroid treatment have a stable or decreasing dose for at least 7 days before the baseline MRI scan.
8)Subjects receiving enzyme-inducing anti-epileptic drug (EIAED) should change to non-enzyme inducing anti-epileptic drug (Non-EIAED) at least 2 weeks before the study enrollment
9)Subjects who are able/willing to use adequate contraceptive methods, including barrier method (male condom or diaphragm with a spermicide, or cervical cap) for the duration of the study and for at least 6 months after the last dose of the investigational product (For male, should agree to contraception and not to donate sperm for 6 months after the last dose of bevacizumab)
1)Malignancies other than disease under study within 5 years prior to the first dose of study drug, except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ)
2)Subjects who have received bevacizumab or other VEGF inhibitors prior to study participation
3)Body Mass Index (BMI) = 30 kg/m2
4)Subjects confirmed intracranial hemorrhage with non-contrast CT or MRI
5)Bleeding diathesis or coagulopathy
6)Clinically significant cardiovascular disease, such as cerebrovascular accidents or myocardial infarctions within 6 months prior to enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater CHF, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with study treatment
7)History of arterial or venous thromboembolism 6 months prior to study participation
8)Uncontrolled hypertension (blood pressure = 150/90 mmHg with appropriate antihypertensive therapy)
9) History of hypertensive crisis or hypertensive encephalopathy
10)Subjects receiving therapeutic anticoagulation (except low molecular weight heparin or warfarin)
11)Pregnancy or breastfeeding. Subjects who will stop breastfeeding before the study participation will not be excluded (women of childbearing potential † must have negative serum pregnancy test during the screening period prior to study participation)
† Women of childbearing potential: females have had menarche and not achieved post-menopausal status, defined as cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and have not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy)
12)Subjects with active virus infection requiring systemic treatment at screening
?Positive test for HIV infection
?Subjects positive for anti-HBsAg Infected with active HBV hepatitis, defined as HBsAg positive during the screening. But, subjects infected with historical or resolved HBV hepatitis (acute or chronic), defined as HBsAg negative and HBcAb positive during the screening can participate in the study with the HBV DNA test result of negative or not detected.
?Active HCV hepatitis: positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. But the subject can be enrolled with serum anti-HCV positive and HCV RNA negative
13)Subjects with autoimmune disease/ syndromes requiring treatment at the time of screening (Appendix 2. List of autoimmune disease)
?Subjects receiving the following alternative therapies can participate in the study at the Investigator’s discretion: Corticosteroid replacement therapy for adrenal or pituitary insufficiency requiring physiological dose of corticosteroids such as thyroxine, insulin
?Subjects with leukoplakia, resolved pediatric asthma, atopic dermatitis, type 1 diabetes, hypothyroidism due to autoimmune disease only requiring hormone replacement therapy, psoriasis not requiring systemic treatment, and other disease status that recurrence nor exacerbations are not expected unless there is external contributing factors can participate in the study
14) Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the stu
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) by iRANO criteria;Overall survival
- Secondary Outcome Measures
Name Time Method ORR (Objective response rate) by iRANO criteria;DOR (Duration of response) by iRANO criteria;DCR (Disease control rate) by iRANO criteria;Incidence of adverse events (AEs) graded according to NCI CTCAE v5.0;Incidence of anti-drug antibodies (ADAs) ;Incidence of anti-neutralizing antibody;Changes of ALC (absolute lymphocyte count);Changes of absolute counts and ratios of immune cell subtypes