Phase II study of avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (Tide-A study).
- Conditions
- metastatic renal cell carcinomaMedDRA version: 21.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004098-23-IT
- Lead Sponsor
- CONSORZIO ONCOTECH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 75
Each patient must meet the following criteria to be enrolled in this study.
1.Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected.
2.Availability of tumor tissue sample for biomarker analysis.
3.Male or female subjects aged = 18 years
4.At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
5.Eastern Cooperative Oncology Group performance status 0 or 1.
6.Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment:
I.Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L).
II.Platelets = 100,000/mm3 (= 100 GI/L).
III.Hemoglobin = 9 g/dL (= 90 g/L).
IV.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × upper limit of normal.
V.Total bilirubin = 1.5 × the upper limit of normal. For subjects with Gilbert’s disease = 3 mg/dL (= 51.3 µmol/L).
VI.Serum creatinine = 2.0 × upper limit of normal or calculated creatinine clearance = 30 mL/min (= 0.5 mL/sec) using the Cockroft-Gault.
7.Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
8.Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for at least 30 days after the last dose of study treatment. Acceptable methods are provided in Appendix E.
9.Negative serum or urine pregnancy test at screening for women of childbearing potential.
Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons. A lactating woman should be advised to not to breastfeed during treatment and for at least one month after the last dose of avelumab.
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1.Prior treatment with systemic therapy for advanced RCC
2.Prior adjuvant or neoadjuvant therapy
3.Bulky or symptomatic disease or hepatic metastases.
4.Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
5.Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
6.Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment 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 prostate cancer (=pT2,N0; Gleason 6) with no plans for treatment intervention.
7.Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the start of treatment. Systemic treatment with radionuclides within 6 weeks before the start of treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
8.Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of treatment.
9.Concomitant anticoagulation at therapeutic doses with oral anticoagulants
10.In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
11.Chronic treatment with corticosteroids or other immunosuppressive agents . Subjects with brain metastases requiring systemic corticosteroid are not eligible.
12.The subject has uncontrolled, significant intercurrent or recent illness
13.Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before the start of treatment. Complete wound healing from major surgery must have occurred 1 month before the start of treatment and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before the start of treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
14.Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month before the start of treatment
15.Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
16.Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
17.Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
18.History of substance abuse or medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
19.Illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the stu
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