A Phase 1/2, Multiple-dose, Dose-escalation Study to Assess the Safety, Efficacy, and Pharmacokinetics of Intravenous CNTO 328, an Anti-interleukin 6 (IL-6) Monoclonal Antibody, in Subjects with Solid Tumors
- Conditions
- Malignant solid tumorsMedDRA version: 9.1Level: LLTClassification code 10065147Term: Malignant solid tumor
- Registration Number
- EUCTR2008-005180-33-BE
- Lead Sponsor
- Janssen Biologics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
To be eligible for the study, subjects must meet all of the following criteria:
1. Age = 18 years old.
2. Have capacity to understand and provide signed and dated informed consent prior to any study specific-procedures and agree to comply with all protocol-specified procedures.
3. Histologic or cytologic documentation of malignancy as follows:
a. Phase 1 Pharmacokinetic (Cohort 1) and dose-escalation (Cohorts 2 through 4): Subjects with malignant solid tumors that have progressed on or after standard therapy, or for which there is no effective therapy.
b. Phase 1 expansion Cohort 5: Subjects with solid tumors of the subtypes
described.
1) Epithelial ovarian cancer subject who progressed on or after standard therapy. Subjects should be platinum resistant and taxane resistant, defined as, progression on or within 6 months of completing therapy with taxane and platinum either alone or in combination (unless contraindications for taxane or platinum exist), and for which there is no effective therapy.
2) Subjects with known K-Ras mutant tumors or pancreatic cancer, or NSCLC, CRC or head and neck (H&N) cancer that are refractory or resistant to anti-EGFR therapy. All subjects must have received at least 1 line of standard chemotherapy.
c. Phase 2 ovarian cancer cohort: Subjects with epithelial ovarian cancer, who progressed on or after standard therapy. Subjects should be platinum resistant and taxane resistant, defined as progression on or within 6 months of completing therapy with taxane and platinum either alone or in combination (unless contraindications for taxane or platinum exist), and for which there is no effective therapy.
d. Phase 2 K-Ras mutant cohort: Subjects with known K-Ras mutant tumors or subjects with pancreatic cancer, or subjects with NSCLC, CRC or head and neck (H&N) cancer that are refractory or resistant to anti-EGFR therapy. All subjects must have received at least 1 line of standard chemotherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status score = 2.
5. Subjects must have recovered from reversible toxicity of previous treatment to = Grade 1 or an acceptable baseline.
6. Subjects of childbearing potential must use adequate birth control measures. Negative pregnancy test (urinary beta human chorionic gonadotropin [ß-HCG]) at screening (applicable to women of child bearing potential who are sexually active).
7. Adequate bone marrow, liver, and renal function:
a. Hb = 9.0 g/dL (5.6 mmol/L; 90 g/L)
b. Absolute neutrophil count = 1.5 x 109/L (1500/mm3)
c. Platelets = 75 x 109/L
d. CrCL > 20 mL/min estimated by formula
e. Liver function tests:
1) Aspartate transaminase [AST], alanine transaminase [ALT]): = 2.5 x upper limit of normal [ULN] if no liver metastasis; = 5 x ULN with liver metastasis
2) Total bilirubin = 1.5 x ULN or = 3x ULN if due to tumor obstruction
3) Alkaline phosphatase = 3 x ULN if no liver metastasis or bone involvement, and = 5 x ULN with liver metastasis or bone involvement
f. Coagulation prothrombin time/international normalized ratio (PT/INR) and
activated partial thromboplastin time (aPTT) within 1.5 x ULN
8. For the expansion Cohort 5 and Phase 2 ovarian cancer and K-Ras mutant tumor cohorts: evaluable or measurable disease (defined by RECIST, as applicable)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number o
Subjects meeting any of the following criteria may not be enrolled in the study:
1. Received any prior systemic therapy:
• Bevacizumab: within 12 weeks prior to the first CNTO 328 administration
• Nitrosoureas and mitomycin C: within 6 weeks prior to the first CNTO 328
administration
• All other prior systemic therapy or major surgery for the cancer under study:
within 4 weeks prior to the first CNTO 328 administration.
Concomitant use of immunotherapy, biotherapy, radiotherapy, chemotherapy,
investigative therapy, immunosuppressive therapy, or IL-6 modulating agents is
prohibited during the study except for stable low-dose steroids or luteinizing
hormone-releasing hormone (LHRH) agonists in prostate cancer subjects.
2. Previous anti IL-6 targeted therapy.
3. Serious concurrent illness or history of uncontrolled heart disease such as: unstable angina, congestive heart failure, myocardial infarction within preceding 12 months, clinically significant rhythm or conduction abnormality.
4. Subjects with known allergies or clinically significant reactions to murine,
chimeric, or human proteins.
5. For the dose expansion Cohort 5, ovarian cancer and K-Ras mutant tumor cohorts: Prior malignancy (other than the 1 under study) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the subject has been disease-free for = 5 years).
6. Clinically significant active infection within 2 weeks prior to the first CNTO 328
administration.
7. Evidence of bleeding disorder.
8. Pregnant or lactating women.
9. Any uncontrolled medical condition, including the presence of laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study.
10. Known central nervous system (CNS) metastases.
11. Known infection with human immunodeficiency virus (HIV), known hepatitis C infection or known to be hepatitis B surface antigen positive.
12. Subjects cannot be vaccinated with live, attenuated vaccines during the following time period: Within 4 weeks of the first administration of CNTO 328 and from the first administration of study agent to 12 weeks after the last administration of CNTO 328.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method