A Study of Avelumab In Combination with Axitinib Versus Sunitinib In Patients With Advanced Kidney Cancer
- Conditions
- Advanced renal cell carcinoma (aRCC)MedDRA version: 21.0Level: LLTClassification code 10023405Term: Kidney cancer stage IVSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10023404Term: Kidney cancer stage IIISystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002429-20-IT
- Lead Sponsor
- PFIZER INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 583
•Histologically or cytologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component. Advanced RCC patients are patients affected by unresectable disease either unresectable locally advanced or metastatic disease;
•A formalin fixed, paraffin embedded (FFPE) tumor tissue block from a de novo tumor biopsy obtained during screening will be required (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of randomization AND 2) the patient has not received any intervening systemic anti cancer treatment from the time the tissue was obtained and randomization onto the current study. If an FFPE tissue block cannot be provided as per documented regulations then 15 unstained slides (10 minimum) will be acceptable
•Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided as per documented regulations,then 15 unstained slides (10 minimum) will be acceptable;
•At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
2.Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative, as allowed by local guideline/practice) has been informed of all pertinent aspects of the study.
3.Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
4.Age ¿18 years (¿20 years in Japan).
5.Estimated life expectancy of at least 3 months.
6.ECOG PS 0 or 1.
7.No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure (BP) readings taken at least 1 hour apart. The baseline systolic BP readings must be ¿140 mm Hg, and the baseline diastolic BP readings must be ¿90 mm Hg. Use of antihypertensive medications to control BP is allowed.
8.Adequate bone marrow function, including:
•Absolute Neutrophil Count (ANC) ¿1,500/mm3 or ¿1.5 x 10/L;
•Platelets ¿100,000/mm3 or ¿100 x 10/L;
•Hemoglobin ¿9 g/dL (may have been transfused).
9.Adequate renal function, including:
•Estimated creatinine clearance =30 mL/min as calculated using the Cockcroft Gault (CG) equation.
•Urinary protein <2+ by urine dipstick. If dipstick is ¿2+, then 24 hour urinary protein <2 g per 24 hours.
10.Adequate liver function, including:
•Total serum bilirubin ¿1.5 x ULN;
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ¿2.5 x ULN.
11.Left ventricular ejection fraction (LVEF) = lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO).
12.Serum pregnancy test (for females of childbearing potential) negative at screening.
13.Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 90 days after the last dose of assigned treatment
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 408
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this ag
•Prior systemic therapy directed at advanced or metastatic RCC.
•Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment.
•Prior immunotherapy with IL 2, IFN a, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.
•Prior therapy with axitinib and/or sunitinib as well as any prior therapies with other VEGF pathway inhibitors.
2.Participation in other therapeutic studies within 4 weeks prior to randomization.
3.Patients with known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
4.Major surgery ¿4 weeks or major radiation therapy ¿2 weeks prior to randomization. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 48 hours prior to patient randomization.
5.Persisting toxicity related to prior therapy NCI CTCAE v4.0 Grade >1; however, sensory neuropathy Grade =2 is acceptable.
6.Current or prior use of immunosuppressive medication within 7 days prior to randomization, except the following:
•Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection);
•Systemic corticosteroids at physiologic doses =10 mg/day of prednisone or equivalent;
•Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
7.Known severe hypersensitivity reactions to monoclonal antibodies (Grade ¿3), any history of anaphylaxis..
8.Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
9.Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration).
10.Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
11.Gastrointestinal abnormalities including:
•Inability to take oral medication;
•Requirement for intravenous alimentation;
•Prior surgical procedures affecting absorption including total gastric resection;
•Treatment for active peptic ulcer disease in the past 6 months;
•Active gastrointestinal bleeding, unrelated to cancer, as evidenced by clinically significant hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
•Malabsorption syndromes.
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