Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title A Phase II study of the efficacy and safety of Axitinib given on an individualized schedule for metastatic renal cell cancer after treatment with PD-1 or PD-l1 inhibitor
IRB CASE 7815
CC 15-1386
Hospital Main Campus
Phase Phase 2
Disease Renal
Drug Axitinib
Description
Primary objective- To determine whether axitinib given on an individualized dose/schedule for metastatic renal cell carcinoma following immunotherapy with PD-1 and PD-L1 Inhibitors leads to improved PFS.
- To characterize the objective response rates in patients given axitinib on an individualized dose/schedule
- To evaluate the tolerability and safety of an alternative method of axitinib titration.
- To characterize the anti-tumor effect, as measured by change in tumor burden per RECIST 1.1, of axitinib titration performed after initial RECIST PD on axitinib
Inclusion Criteria
- Histologically confirmed, locally recurrent or metastatic clear cell renal cell carcinoma
- Has received one prior systemic therapy regimen for mRCC directed against PD-1 and/or PD-L1 which must have been the most recent regimen
- Prior high-dose interleukin-2 therapy is permitted in addition to anti-PD(L)1 therapy, but is not required
- Prior bevacizumab or VEGF TKI is permitted either in combination with anti-PD(L)1 therapy OR as monotherapy when given PRIOR to anti-PD(L)1 therapy
- Only ONE prior VEGF-based therapy (bevacizumab or VEGF TKI) is permitted.
- Prior treatment with combined ipilimumab and nivolumab is permitted
- Prior axitinib in any setting is not permitted
- Prior neoadjuvant or adjuvant therapy is permitted if disease recurrence was greater than 6 months from the last dose of therapy.
- Evidence of measurable disease per RECIST 1.1.
- Male or female, age ≥ 18 years
- Karnofsky performance status ≥ 70 %.
- Adequate organ function as defined by:
- Absolute neutrophil count (ANC) &ge 1,000/μL
- Platelets &ge 100,000/μL
- Hemoglobin &ge 9.0 g/dL
- Serum calcium ≤ 12.0 mg/dL
- Serum Creatinine ≤ 2.0 x ULN
- Total serum bilirubin ≤ 1.5 x ULN
- SGOT ≤ 2.5 x ULN and SGPT ≤ 2.5x ULN
- Signed informed consent and willingness/ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Exclusion Criteria
- More than 1 VEGF-based systemic therapy, given either as monotherapy or in combination with anti-PD(L)1 therapy
- Non clear cell RCC
- Major surgery within 4 weeks of starting the study treatment.
- Radiation therapy within 2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
- NCI CTCAE Version 4.03 grade 3 hemorrhage within 4 weeks of starting the study treatment (Section 15.4).
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
- Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.03 grade ≥ 2. Controlled atrial fibrillation is permitted.
- Prolonged QTc interval on baseline EKG (>450 msec for males or >470 msec for females)
- Uncontrolled hypertension (>160/100 mm Hg despite optimal medical therapy)
- Concurrent treatment on another clinical trial. Supportive care trials or nontreatment trials, e.g. QOL, and imaging trials, are allowed.
- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
- Uncontrolled CNS metastases. Patients are considered to have controlled CNS metastases (and thus eligible) if they have completed local therapy (XRT and/or surgery) and are off steroids with clinical and radiographic stability 1 month from the end of CNS-directed therapy.