Metastatic Renal Cell Carcinoma (RCC) MedDRA version: 8.1 Level: HLT Classification code 10038408 Term: Renal cell carcinomas
Conditions
Interventions
Trade Name: Remicade
Pharmaceutical Form: Powder for solution for infusion
Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
Sponsors
The Royal Marsden NHSF Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. 2. The presence of one or more clinically or radiologically measurable lesions 3. ECOG performance status 0 or 1 4. Life expectancy greater than 12 weeks 5. At least 21 days since major surgery and 7 days since skin/tumour biopsy 6. The capacity to understand the patient information sheet and the ability to provide written informed consent 7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures 8. Male or female, age 18 or greater 9. Women must be postmenopausal (no menstrual period for a minimum of 1 year) or have a negative serum pregnancy test on entry in the study (even if surgically sterilized). Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last study treatment 10. Serum aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 x upper limit of normal (ULN) 11. Total serum bilirubin =1.5 x ULN 12. Serum creatinine =1.5 x ULN 13. Haemoglobin =9.0 g/dL 14. Absolute neutrophil count =1.5 x 109/L 15. Platelets =100 x 109/L 16. Prothrombin time (PT) =1.5 x ULN 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 of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous treatment with monoclonal antibodies or antibody fragments, or known hypersensitivity to any murine proteins or other infliximab components 2. Known infection with human immunodeficiency virus (HIV) and / or hepatitis B surface antigen or hepatitis C 3. Known history of serious infections (e.g. hepatitis, pneumonia or pyelonephritis) in the previous 3 months 4. Opportunistic infections (e.g. herpes zoster (shingles), cytomegalovirus, active pneumocystis carinii, aspergillosis, histoplasmosis, or atypical mycobacteria infection other than TB) within the last 6 months 5. History of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g. nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area) or splenomegaly# 6. Current signs or symptoms of severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC 7. Intracranial disease, unless there has been radiological evidence of stable intracranial disease > 6 months. In the case of a solitary brain metastasis, evidence of a disease-free interval of at least 3 months post surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days 8. Previous treatment with a tyrosine kinase inhbitor or anti-angiogenic agent (licensed or investigational) such as sunitinib or bevacizumab 9. Any drug (licensed or investigational) that targets the RAS or EGFR pathway 10. Any chemotherapy, immunotherapy or hormonal treatment over the last 4 weeks. Palliative radiotherapy to symptomatic disease sites is permitted 11. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last treatment (this includes men who plan to father a child within 6 months of the last treatment) 12. Chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB as described in Appendix C 13. Ineligibility according to the TB eligibility assessment, screening, and early detection of reactivation rules (see Appendix C) 14. Malignancy other that the condition being treated or a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence 15. Use of any investigational drug within 30 days prior to screening or within 50 days of infliximab infusion 16. Presence of a transplanted solid organ (with the exception of a corneal transplant) > 3 months prior to screening 17. History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results 18. Peripheral neuropathy greater than grade 1 according to the Common Terminology Criteria (CTC) criteria 19. Concomitant diagnosis or history of congestive heart failure as assessed by the investigator 20. Uncontrolled hypertension or hypertension treated with 2 or more anti-hypertensive agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a phase I / II design. The objective of the phase I section is to define a safe and tolerable dose of infliximab and sorafenib in combination and to assess its pharmacokinetics and pharmacodynamics. The objective of the phase II section is to assess safety and efficacy of the combination in a Simon 2 stage design. The primary efficacy variable will be the proportion of patients progression free after 6 months of treatment. ;Secondary Objective: Secondary efficacy variables will be 1. Pharmacokinetics of the combination of infliximab and sorafenib 2. Changes in predictive biomarkers and pharmacodynamic markers induced by the combination of infliximab and sorafenib 3. Response rate at 12 weeks of treatment and best response to therapy 4. Overall survival median and 95% Confidence Interval, CI; also PFS median and 95% CI. 5. Correlation of biological markers in original nephrectomy specimen (if available) or on-study biopsies with clinical outcome and serum biomarkers such as TNF?? IL-6 and CCL2 ;Primary end point(s): Phase I: Doses of infliximab and sorafenib in combination that are safe and tolerable Phase II: Proportion of patients progression free at six months | — |
Countries
United Kingdom
Outcome results
None listed