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Study to Evaluate Efficacy and Safety of Sunitinib in Renal Cell Carcinoma Progressed to 1L Immunotherapy Treatment. (INMUNOSUN)

Primary Purpose

Clear Cell Renal Carcinoma

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Sunitinib

About this trial

This is an interventional treatment trial for Clear Cell Renal Carcinoma focused on measuring Clear Cell Renal Carcinoma, Sunitinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, anti-PDL1 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 adverse event(s) are clinically nonsignificant and/or stable on supportive therapy.
7. Eastern Cooperative Oncology Group 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 × upper limit of normal (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.

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. Corrected QT interval (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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sunitinib

Arm Description

Sunitinib 50 mg/day, 4 weeks on/2weeks off

Outcomes

Primary Outcome Measures

Objective response rate

Percentage of patients with documented response according RECIST 1.1 criteria (complete response + partial response)

Secondary Outcome Measures

Progression-free survival

Time from start of treatment to disease progression or death.

Time to progression

Time from start of treatment to disease progression or death due to the illness

Duration of the response

Time from first response to disease progression or death.

Overall survival

Time from start of treatment to death.

Clinical benefit

Percentage of patients with documented response or disease stabilization according RECIST 1.1 criteria

Number of individual events (hematologic events and not hematologic events)

Percentage of patients with each of the adverse event per grade

Full Information

NCT ID

NCT03066427

First Posted

February 23, 2017

Last Updated

November 12, 2020

Sponsor

Spanish Oncology Genito-Urinary Group

Collaborators

Pfizer, Apices Soluciones S.L.

1. Study Identification

Unique Protocol Identification Number

NCT03066427

Brief Title

Study to Evaluate Efficacy and Safety of Sunitinib in Renal Cell Carcinoma Progressed to 1L Immunotherapy Treatment.

Acronym

INMUNOSUN

Official Title

Phase II Study to Evaluate Efficacy and Safety of Sunitinib Therapy in Patients With Metastatic Renal Clear Cell Carcinoma Who Have Progressed to First-line Immunotherapy Treatment (INMUNOSUN Study)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

May 10, 2017 (Actual)

Primary Completion Date

September 22, 2020 (Actual)

Study Completion Date

September 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Spanish Oncology Genito-Urinary Group

Collaborators

Pfizer, Apices Soluciones S.L.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The therapeutic scenario of metastatic renal cancer is undergoing a new revolution with the appearance of a novel therapeutic strategy after the antiangiogenic treatments, that is the immunotherapy, in addition to the approval of new active drugs in the following lines of treatment. There are currently two phase III trials in the first line of treatment in metastatic renal cancer that include different combinations of treatment based on immunotherapy. If results of these studies were positive, the therapeutic algorithm would be modified so that the remaining drugs would have to be repositioned within the therapeutic decision scheme. Sunitinib has previously demonstrated its benefit in patients who had failed to prior treatment with cytokines, so it is likely to continue to be effective in patients who have become resistant to treatment with new drugs based on immune checkpoint blockade. This phase II study is developed to evaluate the activity of sunitinib after treatment with immunotherapy-based regimens that are currently being developed within phase III clinical trials.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clear Cell Renal Carcinoma

Keywords

Clear Cell Renal Carcinoma, Sunitinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sunitinib

Arm Type

Experimental

Arm Description

Sunitinib 50 mg/day, 4 weeks on/2weeks off

Intervention Type

Drug

Intervention Name(s)

Sunitinib

Other Intervention Name(s)

Sutent

Intervention Description

Sunitinib 50 mg/d

Primary Outcome Measure Information:

Title

Objective response rate

Description

Percentage of patients with documented response according RECIST 1.1 criteria (complete response + partial response)

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

Time from start of treatment to disease progression or death.

Time Frame

12 months

Title

Time to progression

Description

Time from start of treatment to disease progression or death due to the illness

Time Frame

12 months

Title

Duration of the response

Description

Time from first response to disease progression or death.

Time Frame

12 months

Title

Overall survival

Description

Time from start of treatment to death.

Time Frame

18 months

Title

Clinical benefit

Description

Percentage of patients with documented response or disease stabilization according RECIST 1.1 criteria

Time Frame

12 months

Title

Number of individual events (hematologic events and not hematologic events)

Description

Percentage of patients with each of the adverse event per grade

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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, anti-PDL1 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 adverse event(s) are clinically nonsignificant and/or stable on supportive therapy. 7. Eastern Cooperative Oncology Group 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 × upper limit of normal (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. 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. Corrected QT interval (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.

Overall Study Officials: