Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.

Nephrectomy

Patient Observation

Lauren Harshman

This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

PRIMARY OBJECTIVE:

I. To compare recurrence-free survival (RFS) between patients with renal cell carcinoma randomly assigned to perioperative nivolumab in conjunction with radical or partial nephrectomy with patients randomized to surgery alone.

SECONDARY OBJECTIVES:

I. To evaluate for differences in recurrence-free survival associated with perioperative nivolumab compared to surgery alone among the subset of patients with clear cell histology.

II. To compare the overall survival between the two arms. III. To describe the safety and tolerability of perioperative nivolumab.

CORRELATIVE OBJECTIVES:

I. To correlate the primary tumor's expression of PD-L1 with outcome. II. To correlate the expression of PD-L1 on tumor tissue at nephrectomy and recurrence with outcome.

III. To archive images for potential central confirmation of recurrence and for future correlative work with American College of Radiology Imaging Network (ACRIN), including markers predicting outcome or response.

IV. To prospectively collect tumor and biologic specimens (e.g., serum, peripheral blood mononuclear cells \[PBMCs\]) for future correlative studies.

V. To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy.

VI. To characterize the immunogenicity of nivolumab.

QUALITY OF LIFE OBJECTIVE:

I. To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone.

OTHER EXPLORATORY OBJECTIVES:

I. To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.

II. To characterize the effects of nivolumab on bone metabolism and bone density.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and every 12 months for 5 years.

Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Association between the primary tumor's expression of PD-L1 with outcome

Association between the expression of PD-L1 on tumor tissue at nephrectomy as well as recurrence and outcome

To archive images for potential central confirmation of recurrence and for future correlative work

To collect tumor and biologic specimens for future correlative studies

To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy

To characterize the immunogenicity of nivolumab

To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone

To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.

To characterize the effects of nivolumab on bone metabolism and bone density

RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 5 years was the proportion of patients who are recurrence-free and alive at 5 years based on Kaplan-Meier estimates.

RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 3 years was the proportion of patients who are recurrence-free and alive at 3 years based on Kaplan-Meier estimates.

Overall survival is defined as time from randomization to death from any cause. Overall survival rate at 5 years was the proportion of patients who are alive at 5 years based on Kaplan-Meier estimates.

Canadian Cancer Trials Group

National Cancer Institute (NCI)

All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.

Arm A (Nephrectomy + Nivolumab)

Arm B (Nephrectomy Only)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All randomized RCC patients are included in this analysis.

Study Statistician

All randomized RCC patients were included in this analysis.

Recurrence-free Survival (RFS) Rate at 5 Years

All randomized RCC patients who had clear cell histology according to surgery or biopsy were included in this analysis.

Recurrence-free Survival (RFS) Rate at 3 Years Among Patients With Clear Cell Histology

All randomized patients were included in this analysis.

Overall Survival Rate at 5 Years

Association Between the Primary Tumor's Expression of PD-L1 With Outcome

Association Between the Expression of PD-L1 on Tumor Tissue at Nephrectomy as Well as Recurrence and Outcome

To Archive Images for Potential Central Confirmation of Recurrence and for Future Correlative Work

To Collect Tumor and Biologic Specimens for Future Correlative Studies

To Characterize the Pharmacokinetics of Nivolumab and Explore Exposure Response Relationships With Respect to Safety and Efficacy

To Characterize the Immunogenicity of Nivolumab

To Evaluate Differences in Change From Baseline in Patient-reported Symptoms and Toxicities Among Patients Randomized to Treatment With Nivolumab Compared to Surgery Alone

To Explore Descriptively the Efficacy of Treatment With Nivolumab in Patients With Non-clear Cell (Including Unclassified) Histologies.

To Characterize the Effects of Nivolumab on Bone Metabolism and Bone Density

Overall Study

Sunitinib

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate PO QD for 4 weeks and placebo sorafenib tosylate PO QD or BID for 6 weeks.

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks followed.

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.

Laboratory Biomarker Analysis

Placebo

Quality-of-Life Assessment

Sorafenib Tosylate

Sunitinib Malate

Naomi S Balzer-Haas

This randomized phase III trial studies sunitinib malate to see how well it works compared to sorafenib tosylate or placebo in treating patients with kidney cancer that has been removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sunitinib malate is more effective than sorafenib tosylate or placebo in treating kidney cancer.

PRIMARY OBJECTIVES:

I. To demonstrate an improvement in disease-free survival in locally advanced renal cell carcinoma patients randomly assigned to adjuvant sunitinib (sunitinib malate) (Arm A) or sorafenib (sorafenib tosylate) (Arm B) versus placebo (Arm C) after radical or partial nephrectomy.

SECONDARY OBJECTIVES:

I. To compare overall survival of patients randomized to each of the two regimens with placebo.

II. To further define the toxicity of prolonged administration of sunitinib or sorafenib in this patient population.

III. To prospectively collect tumor and biological specimens to assess their characteristics and associations: novel approaches to assess angiogenesis markers in tissue, blood and urine as predictors of disease-free survival and of therapeutic benefit.

IV. To prospectively collect tumor and biological specimens to assess their characteristics and associations: the frequency of oncogene and tumor suppressor gene mutations as predictors of disease-free survival and therapeutic benefit.

V. To prospectively collect tumor and biological specimens to assess their characteristics and associations: tumor and genetic polymorphisms as predictors of disease-free survival and therapeutic benefit.

VI. To prospectively collect tumor and biological specimens to assess their characteristics and associations: deoxyribonucleic acid (DNA) methylation profiles as predictors of outcome and of therapeutic benefit.

VII. To prospectively collect tumor and biological specimens to assess their characteristics and associations: The relationship of polymorphisms in drug metabolizing enzymes with steady state concentrations of sorafenib and sunitinib in selected patients.

VIII. To study the effect of vascular endothelial growth factor (VEGF) targeted therapy on circulating endothelial cells and circulating endothelial progenitors.

IX. To prospectively assess patient-reported fatigue in order to compare the magnitude and trajectory of fatigue among renal cell carcinoma (RCC) patients randomized to adjuvant sunitinib (Arm A) or sorafenib (Arm B) to placebo (Arm C). (Quality of life objectives) X. To evaluate the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form (SF)1, a newly developed state-of-the-science PROMIS measure for fatigue and to calibrate the PROMIS Fatigue-SF1 with the established, validated FACIT-Fatigue scale. (Quality of life objectives)

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate orally (PO) once daily (QD) for 4 weeks and placebo sorafenib tosylate PO QD or twice daily (BID) for 6 weeks.

ARM B: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks followed.

ARM C: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.

In all arms, treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery

ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma

PROMIS Fatigue short form is a newly developed state-of-the-science PROMIS measure for fatigue

Disease-free survival (DFS) is defined as time from randomization to recurrence, development of second primary cancer (except localized breast or prostate cancer or nonmelanoma skin cancer), or death from any cause. Patients who were alive without recurrence or qualifying second primary cancer were censored at the date of last disease evaluation.

Overall survival is defined as the time from randomization to death from any cause. Patients without a date of death were censored at the date of last contact. Kaplan-Meier method was used to estimate 5-year survival rate.

Cardiac event is defined as left ventricular ejection fraction (LVEF) below the institutional lower limit of normal, where the decrease was \>15% absolute percentage points from baseline within 6 months.

Disease-free survival (DFS) is defined as time from randomization to recurrence, development of second primary cancer (except localized breast or prostate cancer or nonmelanoma skin cancer), or death from any cause. Patients who were alive without recurrence or qualifying second primary cancer were censored at the date of last disease evaluation. 5-year DFS rate is the proportion of patients who are alive and disease-free at 5 years based on the Kaplan-Meier estimate.

Cancer and Leukemia Group B

NCIC Clinical Trials Group

SWOG Cancer Research Network

Only adverse events that are possibly, probably, or definitely related to protocol therapy are reported.

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.

Arm A (Sunitinib + Sorafenib Placebo)

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.

Arm B (Sorafenib + Sunitinib Placebo)

Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.

Arm C (Sunitinib Placebo + Sorafenib Placebo)

Age, Categorical

Disease-free Survival (DFS)

5-year Overall Survival Rate

Patients with at least 1 follow-up MUGA scan were included in this analysis.

Proportion of Patients With Cardiac Events

Patients with clear cell histology were included in this analysis.

5-year Disease-free Survival (DFS) Rate Among Patients With Clear Cell Histology

The Association Between Angiogenesis Markers and Disease-free Survival

The Association Between Disease-free Survival and the Frequency of Oncogene as Well as Tumor Suppressor Gene Mutations

The Association Between Tumor and Genetic Polymorphisms and Disease-free Survival

The Association Between Deoxyribonucleic Acid (DNA) Methylation Profiles and Disease-free Survival

The Relationship of Polymorphisms in Drug Metabolizing Enzymes With Steady State Concentrations of Sorafenib and Sunitinib in Selected Patients

The Effect of Vascular Endothelial Growth Factor (VEGF) Targeted Therapy on Circulating Endothelial Cells and Circulating Endothelial Progenitors

Patient-reported Fatigue Using Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale

Patient-reported Fatigue Using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form

The Association Between Scan Frequency and Development of Congestive Heart Failure

Frequency of Clinically Significant Congestive Heart Failure (CHF) Grade 3 or Higher Using the Common Terminology Criteria for Adverse Events Version 4.0

Patients receive nivolumab IV over 30 minutes on days -56, -42, -28, and -14 in the absence of disease progression or unacceptable toxicity. Patients then undergo nephrectomy or metastasectomy on day 0.

Metastasectomy

Martin H Voss

This pilot phase I trial studies the side effects of nivolumab and how well it works in treating patients with high-risk kidney cancer before surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To study the safety and feasibility of preoperative nivolumab administration in subjects with resectable, high-risk, non-metastatic and metastatic renal cell carcinoma undergoing planned cytoreductive nephrectomy or metastasectomy.

SECONDARY OBJECTIVES:

I. To assess overall response rate in patients receiving preoperative nivolumab.

II. To assess recurrence free survival at 2 years in patients receiving preoperative nivolumab in patients with high-risk, non-metastatic disease.

EXPLORATORY OBJECTIVES:

I. To evaluate the association between baseline tumor mutational burden and both immune infiltration and radiographic tumor response to nivolumab.

II. To explore predicted and expressed tumor neoantigens and their correlation with radiographic tumor response to nivolumab.

III. To explore the association between the predicted immune signature (via ribonucleic acid sequencing \[RNAseq\]) in the tumor microenvironment with radiographic tumor response to nivolumab.

IV. To determine whether changes in the tumor microenvironment before, during, and after therapy are associated with response.

V. To assess the potential association between PD-L1 expression (by immunohistochemistry \[IHC\]) and radiographic tumor response to nivolumab.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on days -56, -42, -28, and -14 in the absence of disease progression or unacceptable toxicity. Patients then undergo nephrectomy or metastasectomy on day 0.

After completion of study treatment, patients are followed up at 14-28 days, at 90 days, and then at 24-28 months.

Nivolumab in Treating Patients With High-Risk Kidney Cancer Before Surgery

A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma

Will be defined as ability to procure sufficient quantity and quality of tumor tissue and peripheral blood for testing. Will be descriptive or graphical in nature, and are designed to generate new hypotheses to be tested in future clinical studies. When parameters of immune response are measured, continuous variables will be summarized with means and standard deviations. Dichotomous and categorical variables will be summarized using proportions with exact 95% confidence intervals and counts, respectively. For each patient, comparisons in the pre and post-nivolumab responses will be compared using paired t-tests (or Wilcoxon signed rank tests if appropriate) for continuous variables.

Significant delay is defined as delay of \> 112 days after the first dose of nivolumab, which would constitute a doubling of the 'planned delay' that our design requires for administration of preoperative therapy (56 days).

Will be defined per Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). All patients who receive any amount of the study drug will be evaluable for toxicity. Toxicity will be summarized according to grade as a number and percentage of participants. Each adverse event will be summarized as the highest grade experienced for an individual patient. Descriptive statistics will be used for summaries of the reported toxicity.

Defined per Clavien-Dindo Complications score.

Will be measured by radiographic response assessment for each cross sectional scan obtained using Response Evaluation Criteria in Solid Tumors 1.1. All patients will be categorized per their best radiographic response (complete response/partial response/stable disease/progressive disease), and the frequency of each category will be determined. The overall response rate will be calculated by dividing the sum of all patients achieving a complete response or confirmed partial response by the number of all evaluable patients.

Recurrence free survival will be estimated using the Kaplan-Meier method. Two-year recurrence free survival will be provided along with 95% confidence interval. Patients who are unable to undergo nephrectomy or metastasectomy for any reason will not be included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy	NCT03055013	Metastatic Rena... Sarcomatoid Ren... Stage II Renal ... Stage III Renal... Unclassified Re...	Nephrectomy Nivolumab Patient Observa...	18 Years -	National Cancer Institute (NCI)
Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery	NCT00326898	Clear Cell Rena... Stage I Renal C... Stage II Renal ... Stage III Renal...	Laboratory Biom... Placebo Quality-of-Life... Sorafenib Tosyl... Sunitinib Malat...	18 Years -	National Cancer Institute (NCI)
Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy	NCT03055013	Metastatic Rena... Sarcomatoid Ren... Stage II Renal ... Stage III Renal... Unclassified Re...	Nephrectomy Nivolumab Patient Observa...	18 Years -	National Cancer Institute (NCI)
Nivolumab in Treating Patients With High-Risk Kidney Cancer Before Surgery	NCT02595918	Clear Cell Rena... Metastatic Rena... Stage I Renal C... Stage II Renal ... Stage III Renal... Stage IV Renal ...	Metastasectomy Nephrectomy Nivolumab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage ii renal cell cancer ajcc v7