Status and phase
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About
This phase II open label trial randomized patients who completed the induction with nivolumab plus ipilimumab without complete response or progressive disease will be randomized 1:1 to receive axitinib in addition to nivolumab (Arm A) or continue with nivolumab alone (Arm B).Treatment will be continued until progression of disease, unacceptable toxicity, patient's refusal, or physician decision whichever occurred first.
Full description
The present study aims to demonstrate if the addition of axitinib to nivolumab maintenance after nivolumab plus ipilimumab induction can improve the rate of response considering that the incidence of partial response was 32% and 51% in Checkmate214 and Keynote426 trials respectively.
This study requires 106 patients to show an improvement from 30% to 50% of the incidence of partial responses with a power of 80%, and alpha-error 0.10 (one-side p).
Assuming a drop out of 10%, the final estimated number to enroll should be 118 (59 in arm A and 59 in arm B).
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype and candidate to receive nivolumab after nivolumab plus ipilimumab induction as per standard clinical practice.
Completion of the induction of nivolumab and ipilimumab without toxicity ≥ G2 and no complete response or progressive disease.
Male or female subjects aged ≥ 18 years
Available tumor tissue sample.
At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Eastern Cooperative Oncology Group performance status 0 or 1.
Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment:
Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., 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 amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression or other reasons.
Exclusion criteria
Prior treatment with systemic therapy for advanced RCC with the exclusion of the induction of nivolumab and ipilimumab.
Prior adjuvant or neoadjuvant therapy
Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
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 with no plans for treatment intervention.
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.
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.
Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent ≤ 10 mg prednisone if given for disorders other than renal cell cancer). Subjects with brain metastases requiring systemic corticosteroid are not eligible.
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
I. Cardiovascular disorders:
II. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
III. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before the start of treatment.
IV. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
V. Lesions invading major pulmonary blood vessels.
VI. Other clinically significant disorders such as:
Major surgery (e.g., 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 (e.g., 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.
Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month before the start of treatment (see Section 5.5.4 for Fridericia formula). Three ECGs must be performed. If the average of these three consecutive results for QTcF is ≤ 500 msec, the subject meets eligibility in this regard.
Vaccination within 4 weeks of the first dose of nivolumab and while on trials is prohibited except for administration of inactivated vaccines.
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.
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).
Has a 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.
Has illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
Pregnant or lactating females.
Inability to swallow tablets or capsules.
Previously identified allergy or hypersensitivity to components of the study treatment formulations.
Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Primary purpose
Allocation
Interventional model
Masking
118 participants in 2 patient groups
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Central trial contact
Axin Service; Roberto Iacovelli, MD
Data sourced from clinicaltrials.gov
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