Study to evaluate efficacy and safety of sunitinib in patients with renal cell carcinoma who have progressed to first-line immunotherapy treatment

Phase 1

• Conditions: metastatic renal clear cell carcinoma; MedDRA version: 19.1Level: LLTClassification code 10038416Term: Renal clear cell carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004011-12-ES
• Lead Sponsor: SOGUG (Spanish Oncology Genitourinary Group)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-13
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Eighteen years or older on the day of consent
2. Documented histological or cytological diagnosis of renal cell cancer with a clear-cell component.
3. Patient must have progressed to at least one immune check point inhibitor-based therapy (antiPD1, antiPDL1 o antiCTLA4) for the first line
4. Measurable disease per RECIST 1.1 as determined by the investigator
5. The subjects should not present disease that may be subsidiary of surgical treatment, radiotherapy or combined treatment with curative intent.
6. Recovery of toxicities related to any prior treatments to = Grade 1 CTCAE v.4.03, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
7. ECOG Performance Status (PS) 0-2
8. Adequately controlled blood pressure (BP) with or without antihypertensive medication to maintain a BP <150/90 mmHg before the start of study treatment.
9. Adequate marrow function
- Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L).
- Platelets = 100,000/mm3 (= 100 GI/L).
- Hemoglobin = 9 g/dL (= 5,6 mmol/L).
10. Adequate liver function
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN.
- Total bilirubin = 1.5 × ULN.
11. Adequate kidney function: calculated creatinine clearance = 30 mL/min (= 0.5 mL/sec) using the Cockroft-Gault equation
12. Proteinuria <2+ on urine test strip
13. Prothrombin Time (PT) or International Standard Ratio (INR) = 1.2 x ULN.
14. Life expectancy >3 months.
15. Patient able to ingest study drug and meet study follow-up requirements.
16. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception
17. Female subjects of childbearing potential must not be pregnant at screening.
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 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Previous treatments with sunitinib are not permitted for the advanced or localized disease.
2. Major surgery within 3 weeks of patient inclusion
3. Radiation therapy or embolization within 2 weeks of first dose of sunitinib
4. Previous treatment with immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken prior to (3 months) patient inclusion
5. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
6. Current treatment on another clinical trial.
7. Treatment with known potent CYP3A4 inhibitors or inducers or that prolong the QT interval, within 7 days prior to the inclusion.
8. Prior radiation therapy to >25% of the bone marrow.
9. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
10. Any gastrointestinal malabsorption disorder or any other condition that, in the opinion of the investigator, may affect the absorption of sunitinib or increase the risk of bleeding or perforation.
11. Presence of an unhealed wound or active ulcer.
12. Diarrhea grade III/IV in the screening period.
13. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
14. Clinically significant cardio-cerebrovascular disease within 6 months prior to initiation of treatment.
15. Ongoing cardiac dysrhythmias of NCI CTCAE grade =2, atrial fibrillation of any grade that require treatment.
16. QTc interval >500 msec.
17. Active hemoptysis within 6 weeks prior to initiation of study treatment.
18. Evidence of active bleeding or hemorrhagic diathesis.
19. Presence of endobronchial lesions and / or lesions that infiltrate large vessels.
20. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
21. Other clinically significant alterations:
- Known human immunodeficiency virus (HIV) infection.
- Presence of an uncontrolled active infection.
- Presence of uncontrolled or symptomatic hypothyroidism.
- Moderate-severe liver disease (Child Pugh B-C).
- Requirement for hemodialysis or peritoneal dialysis.
- History of solid organ transplantation.
22. Pregnancy or breastfeeding.
23. Any disease that, in the opinion of the investigator, interferes with the patient's ability to participate in the clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the activity of sunitinib in patients with metastatic renal clear cell carcinoma who have progressed to a previous treatment based on immunotherapy (PD-1, PDL-1, CTLA-4 inhibitors).;Secondary Objective: - Progression-free survival<br>- Time to tumor progression<br>- Duration of the response<br>- Overall survival<br>- Clinical benefit<br>- Correlation of efficacy parameters (ORR, clinical benefit, progression-free survival, and overall survival) with clinical outcome in first line immune therapy<br>- Safety of treatment with sunitinib;Primary end point(s): Objective response rate;Timepoint(s) of evaluation of this end point: Every 8 weeks until week 24. Thereafter, every 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Progression-free survival<br>- Time to progression<br>- Duration of the response<br>- Overall survival<br>- Clinical benefit<br>- Safety;Timepoint(s) of evaluation of this end point: Every 8 weeks until week 24. Thereafter, every 12 weeks.