Clinical trial NCT06661720: Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer
Official title: Short TeRm Intensified Pembrolizumab (KEytruda) and Tivozanib for High-Risk Renal Cell Carcinoma - STRIKE
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Clear Cell Renal Cell Carcinoma
Renal Cell Carcinoma (RCC)
Stage II Renal Pelvis Cancer AJCC v8
Stage III Renal Pelvis Cancer AJCC v8
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
First posted: 2024-10-28
Enrollment: 1040
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase III trial compares the effect of adding tivozanib to standard therapy pembrolizumab versus pembrolizumab alone for the treatment of patients with high-risk renal cell carcinoma (RCC). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tivozanib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving pembrolizumab and tivozanib together may work better than pembrolizumab alone in treating patients with RCC.

Detailed description: PRIMARY OBJECTIVE:

I. To compare disease free survival (DFS) as assessed by the investigator for high-risk renal cell carcinoma patients treated with adjuvant pembrolizumab and tivozanib versus those receiving pembrolizumab alone.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) for patients treated with adjuvant pembrolizumab and tivozanib versus those receiving pembrolizumab alone.

II. To assess adverse events in each study arm by Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

BIOBANKING OBJECTIVE:

I. To bank specimens for future unspecified research.

QUALITY OF LIFE (QOL) OBJECTIVES:

I. To compare global quality of life (QOL) for patients treated with pembrolizumab and tivozanib versus those receiving pembrolizumab alone.

II. To compare patient-reported fatigue for patients treated with pembrolizumab and tivozanib versus those receiving pembrolizumab alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive pembrolizumab intravenously (IV) on days 1 and 43 of each cycle, or on days 1, 22, 43 and 64 of each cycle. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial and may undergo tissue biopsy on study.

ARM II: Patients receive pembrolizumab IV on days 1 and 43 of each cycle and tivozanib orally (PO) once daily (QD) on days 1-21, days 29-49, and days 57-77 of each cycle for up to 6 months. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI or CT throughout the trial and may undergo tissue biopsy on study.

After completion of study treatment, patients are followed up every 4 months for 2 years, then every 6 months for 3 years, then every subsequent year for 5 years.

Eligibility criteria: Inclusion Criteria:

* • Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features following complete resection of the primary tumor (radical or partial nephrectomy)

  * Note: Patients with microscopically positive soft tissue or vascular margins without gross residual disease are permitted

    * Intermediate-high risk RCC:

      * pT2 grade 4 or sarcomatoid features, N0M0
      * pT3 any grade N0, M0
    * High-risk RCC

      * pT4, any grade, N0, M0
      * pT, any stage., any grade, N+, M0
    * cM1 no evidence of disease (NED) RCC

      * Participants who have had resection of primary tumor (radical or partical nephrectomy) and resection or definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) at the time of primary tumor removal (synchronous) or ≤1 year from primary tumor removal (metachronous)

        * Surgery (radical or partial nephrectomy or metastasectomy or ablation) \> 4 weeks but =\< 16 weeks prior to study registration with no ongoing complications from surgery
        * No evidence of disease at time of randomization as assessed by investigator by either CT or MRI scan of the brain and chest, abdomen and pelvis
        * No prior systemic treatment for RCC
        * Age \>= 18 years
        * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
        * Absolute neutrophil count (ANC) \>= 1,000/mm\^3
        * Platelet count \>= 100,000/mm\^3
        * Hemoglobin \>= 8 g/dL
        * Total bilirubin =\< 3 x upper limit of normal (ULN)
        * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x upper limit of normal (ULN)
        * Calculated (calc.) creatinine clearance \>= 30 mL/min (using Cockcroft Gault equation or the estimated glomerular filtration rate from the modification of diet in renal disease trial)
        * Urine protein =\< 1+ on urine analysis (UA) or urine protein creatinine ration (UPCR) \< 2mg/mg
        * Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test is required =\< 14 days prior to registration
        * HIV status: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
        * Hepatitis
  * Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with resolved HBV infection, defined as positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antigen (HbsAg), are eligible
  * Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

    * Cardiac Disease: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better
    * No history of myocarditis
    * No history of clinically significant pneumonitis
    * No uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 90 mm Hg) documented on 2 consecutive measurements taken at least 2 hours apart
    * No serious non-healing wound, ulcer or bone fracture within 28 days prior to registration
    * No serious/active infection requiring parenteral antibiotics
    * No moderate or severe hepatic impairment (child-Pugh B or C)
    * No significant bleeding disorders within 1 month prior to registration, for example:
  * Hematemesis, hematochezia or other gastrointestinal bleeding grade 3 or higher
  * Hemoptysis of pulmonary bleeding grade 3 or higher
  * Hematuria or other genitourinary bleeding grade 3 or higher

    * No history of allogeneic organ transplantation
    * No history of allergy of hypersensitivity to study drugs or components
    * No condition requiring systemic treatment with either corticosteroid (\> 10 mg daily or prednisone equivalent) within 14 days of treatment initiation or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids and adrenal replacement doses ≤10 mg daily prednisone equivalent are permitted in absence of active autoimmune disease
    * No active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition associated with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to registration
    * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
    * No patients with a history of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids \> 10 mg/day, or immunosuppressive drugs) with the following exceptions:
  * Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  * Brief (\<7 days) use of systemic corticosteroids is allowed when use is considered standard of care
  * Patients with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded
  * Patients requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded
  * Patients with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: From time of randomization until disease recurrence or death, assessed up to 10 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From time of randomization until death, assessed up to 10 years
measure: Incidence of adverse events (AEs)
timeFrame: From baseline to 10 years after registration
measure: Proportion of patients that tolerate pembrolizumab and tivozanib
timeFrame: From day 1 to 6 months
Other outcomes:
measure: Estimates of treatment effect by sex
timeFrame: Up to 10 years
measure: Estimates of treatment effect by race
timeFrame: Up to 10 years
measure: Estimates of treatment effect by ethnicity
timeFrame: Up to 10 years
Locations:
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Coeur d'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Sandpoint
country: United States
facility: Kootenai Clinic Cancer Services - Sandpoint
state: Idaho
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Dixon
country: United States
facility: Illinois CancerCare-Dixon
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Shiloh
country: United States
facility: Memorial Hospital East
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
state: Illinois
city: Washington
country: United States
facility: Illinois CancerCare - Washington
state: Illinois
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic - Boone
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic - Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic - Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic - Marshalltown
state: Iowa
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Peabody
country: United States
facility: Lahey Medical Center-Peabody
state: Massachusetts
city: Brighton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Brighton
state: Michigan
city: Canton
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Canton
state: Michigan
city: Chelsea
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
state: Michigan
city: Flint
country: United States
facility: Cancer Hematology Centers - Flint
state: Michigan
city: Flint
country: United States
facility: Genesee Hematology Oncology PC
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
state: Michigan
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Farmington
country: United States
facility: Parkland Health Center - Farmington
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Christian Hospital
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Sainte Genevieve
country: United States
facility: Sainte Genevieve County Memorial Hospital
state: Missouri
city: Sullivan
country: United States
facility: Missouri Baptist Sullivan Hospital
state: Missouri
city: Sunset Hills
country: United States
facility: BJC Outpatient Center at Sunset Hills
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Charleston
country: United States
facility: West Virginia University Charleston Division
state: West Virginia
Study officials:
References: