Trial Title:
Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer
NCT ID:
NCT06661720
Condition:
Clear Cell Renal Cell Carcinoma
Renal Cell Carcinoma (RCC)
Stage II Renal Pelvis Cancer AJCC V8
Stage III Renal Pelvis Cancer AJCC V8
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Pelvic Neoplasms
Pembrolizumab
Tivozanib
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given intravenously
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Other name:
Keytruda
Intervention type:
Drug
Intervention name:
Tivozanib
Description:
Given orally
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Intervention type:
Procedure
Intervention name:
MRI
Description:
Undergo MRI
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Other name:
CT Scan
Other name:
CAT Scan
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm 1 (Pembrolizumab)
Arm group label:
Arm 2 (pembrolizumab + tivozanib)
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
November 7, 2024
Completion date:
November 2037
Lead sponsor:
Agency:
Alliance for Clinical Trials in Oncology
Agency class:
Other
Source:
Alliance for Clinical Trials in Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06661720
