Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

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

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Aldesleukin

Interleukin-2

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Participants received high-dose (HD) IL2, 600,000 IU/kg/dose (Prometheus Laboratories Inc.) i.v. every 8 hours for 5 days (maximum of 14 doses) beginning on day 1 and again on day 15. One course generally consisted of 5 days of treatment, 9 days of rest, 5 more days of treatment, and 9 weeks of rest, followed by up to two additional courses of HD IL2 for patients who benefited and tolerated most of the planned IL2 doses. A treatment delay of up to 4 weeks was allowed for resolution of side effects between courses. Patients were eligible to receive a maximum of three courses of treatment.

HD IL2

David F McDermott, MD

Kim Margolin, MD

Walter Urba, MD

Marc Ernstoff, MD

Theodore Logan, MD

Joseph Clark, MD

Janice Dutcher, MD

Michael Wong, MD

Allen Pantuck, MD

Leslie Oleksowicz, MD

Leonard Appleman, MD

Geoffrey Weiss, MD

Jeffrey Sosman, MD

Ulka Vaishampayan, MD

High-dose interleukin 2 (Proleukin, Novartis) (IL-2) is approved by the U.S Food and Drug Administration (FDA) for the treatment of metastatic kidney cancer and is a standard treatment of this disease. At the present time, IL-2 is the only therapy for kidney cancer that can produce a remission of disease that lasts after treatment is completed. However, most patients who receive IL-2 do not benefit and all patients experience potentially dangerous side effects.

Recent research has suggested that certain patients may respond better to IL-2 than others. The Cytokine Working Group is currently conducting a clinical trial that aims to identify and confirm this research and narrow the application of IL-2 to those patients most likely to benefit.

OBJECTIVES:

Primary

* To determine, in a prospective fashion, if the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "good" pathologic predictive features is significantly higher than a historical, unselected patient population.

Secondary

* To determine, in a prospective fashion, the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "poor" pathologic predictive features and to compare this response rate to the response rate of patients with "good" pathologic predictive features.
* To determine if components of other predictive and prognostic models (e.g MSKCI or UCLA criteria) can help to further define the optimal population to receive high-dose IL2 for metastatic renal cell carcinoma.
* To identify features of the baseline immune function (arginine, arginase, T cell zeta chain) of patients with metastatic renal cell carcinoma that are associated with response to high-dose IL-2.
* To identify new proteins or patterns of gene expression that might be associated with high-dose IL-2 responsiveness in order to further narrow the application of IL-2 therapy to those who will benefit the most.

The High-Dose Aldesleukin (IL-2) "Select" Trial for Patients With Metastatic Renal Cell Carcinoma

The High-Dose Aldesleukin (IL-2) "Select" Trial: A Trial Designed to Prospectively Validate Predictive Models of Response to High Dose IL-2 Treatment in Patients With Metastatic Renal Cell Carcinoma

VHL genotype status will be determined based on establish methods.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by investigator assessment of radiographs.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on treatment on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks.. Response status was determined by independent assessment of radiographs.

Overall survival based on the Kaplan-Meier method is defined as the time from treatment start to date of death or censored at the date of last documented contact.

3-year progression-free survival rate is defined as the proportion of patients absent death or progression based on WHO criteria by 3 years since time of treatment start. PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from treatment start to date of disease progression (PD) or death. Per WHO criteria: PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. Participants who were event-free were censored at the date of their last disease evaluation.

City of Hope National Medical Center

Providence Cancer Center, Earle A. Chiles Research Institute

Dartmouth-Hitchcock Medical Center

Indiana University

Loyola University

Our Lady of Mercy Medical Center

Roswell Park Cancer Institute

University of California, Los Angeles

University of Cincinnati

University of Pittsburgh

University of Virginia

Vanderbilt University

Wayne State University

Dana-Farber Cancer Institute

Beth Israel Deaconess Medical Center

Principal Investigator

Serious AEs: AE that results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly or birth defect; or is an important medical event when, based upon appropriate medical judgment, it may jeopardize the participant and require medical or surgical intervention to prevent one of the above outcomes. Other AEs: Remaining AEs (max grade) with trt-attribution of possibly, probably or definitely.

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Favorable

Intermediate

Poor

Memorial Sloan Kettering Cancer Center (MSKCC) Risk Group: MSKCC developed a nomogram that is used to classify patients into 3 renal cell carcinoma (RCC) 5-year disease recurrence risk groups (low, intermediate, and high) using data from patients treated at MSKCC. The components of the nomogram include RCC histology, disease symptoms, pT stage, and tumor size.

MSKCC Risk Group

High

University of California Los Angeles (UCLA) Survival After Nephrectomy and Immunotherapy (SANI) score: This tool also predicts RCC patient's survival based on lymph node status, metastases, sarcomatoid feature, and TSH level. Patients are classified into 3 groups (low, intermediate, and high). \[Leibovich et al. Cancer 2003\]

UCLA SANI Score

Good

Unknown

ISM \[Atkins et al CCR 2005\] Pathology \[Upton et al. J Immunother 2005\] CAIX (carbonic anhydrase IX) \[Bui et al. CCR 2003\]

Poor: Poor predictive pathology OR the combination of intermediate predictive pathology and low CAIX staining Good: Good predictive pathology OR the combination of intermediate predictive pathology and high CAIX staining

ISM Risk Group

The analysis dataset is comprised of all treated participants.

David F. McDermott, MD

ISM \[Atkins et al CCR 2005\]:

Good predictive pathology OR the combination of intermediate predictive pathology and high CAIX staining

Pathology \[Upton et al. J Immunother 2005\] Good predictive pathology: clear-cell histology AND no papillary features AND \>50% alveolar features AND no granular features Intermediate predictive pathology: clear-cell histology AND no papillary features AND some (\>0%) alveolar features AND 50% granular features

CAIX \[Bui et al. CCR 2003\] High CAIX staining: \>85% of CAIX positive tumor cells

ISM Good Risk Group

The analysis dataset is comprised of all treated patients with available tumor tissue/data for ISM analysis and classified as ISM good risk.

Objective Response in ISM Good Risk Group

Objective response rates were compared between ISM good and poor risk subgroups. ISM good risk ORR reported under primary endpoint.

ISM \[Atkins et al CCR 2005\]:

Poor predictive pathology OR the combination of intermediate predictive pathology and low CAIX staining

Pathology \[Upton et al. J Immunother 2005\] Poor predictive pathology: non-clear-cell histology OR some (\>0%) papillary features OR no alveolar features OR \>50% granular features Intermediate predictive pathology: clear-cell histology AND no papillary features AND some (\>0%) alveolar features AND 50% granular features

CAIX \[Bui et al. CCR 2003\] Low CAIX staining: \</=85% of CAIX positive tumor cells

ISM Poor Risk Group

The analysis dataset is comprised of all treated patients with available tumor tissue/data for ISM analysis and classified as ISM poor risk.

Objective Response Rate in ISM Poor Risk Group

Test against the historical ORR was conducted in the overall study population as secondary analyses.

The analysis dataset is comprised of all treated patients.

Objective Response Rate (Independent Assessment)

Overall Survival

3-Year Progression-Free Survival Rate

Objective response rates were compared between MSKCC subgroups.

MSKCC developed a nomogram that is used to classify patients into 3 renal cell carcinoma (RCC) 5-year disease recurrence risk groups (low, intermediate, and high) using data from patients treated at MSK. The components of the nomogram include RCC histology, disease symptoms, pT stage, and tumor size.

Favorable MSKCC Risk Group

Intermediate MSKCC Risk Group

Poor MSKCC Risk Group

The analysis dataset is comprised of all treated patients with available tumor tissue/data.

Objective Response Rate by MSKCC Risk Group

This tool predicts RCC patient's survival based on lymph node status, metastases, sarcomatoid feature, and TSH level. Patients are classified into 3 groups (low, intermediate, and high).

Low UCLA SANI Score

Intermediate UCLA SANI Score

High UCLA SANI Score

Objective Response Rate by UCLA SANI Score

Objective response rates were compared between tumor type subgroups

Clear Cell Tumor Type

Non-clear Cell Tumor Type

Objective Response Rate by Tumor Type

Objective response rates were compared between clear cell histology subgroups

Good Clear Cell Histology Risk Group

Intermediate Clear Cell Histology Risk Group

Poor Clear Cell Histology Risk Group

Objective Response Rate by Clear Cell Histology Risk Group

Objective response rates were compared between CA-9 score subgroups

This score is based on the expression of the CA 9 protein (encoded by the CA9 gene) assessed from patient's tumor specimen. CA 9 expression score is quantified by immunohistochemical analysis using CA9 monoclonal antibody (M75); High is \>85% of CAIX positive tumor cells.

High CA-9 Score

This score is based on the expression of the CA 9 protein (encoded by the CA9 gene) assessed from patient's tumor specimen. CA 9 expression score is quantified by immunohistochemical analysis using CA9 monoclonal antibody (M75); Low is \</=85% of CAIX positive tumor cells

Low CA-9 Score

Objective Response Rate by CA-9 Score (CAIX Classification)

Objective response rates were compared between PD-L1 tumor subgroups

PD-L1 Tumor Negative

PD-L1 Tumor Positive

Objective Response Rate by PD-L1 Tumor

Objective response rates were compared between B7-H3 tumor subgroups

Negative

Positive

Objective Response Rate by B7-H3 Tumor

Objective response rates were compared between CA-9 SNP subgroups

Patient's SNP (Single Nucleotide Polymorphism) status is determined by sequencing their tumor specimens. Patients are classified as homozygous or variant based on the observed nucleotide sequence.

CA-9 SNP Homozygous

CA-9 SNP Variant

Objective Response Rate by CA-9 SNP

Progression-Free Survival

VHL Genotype Status

Serum arginine levels will be determined based on establish immunohistochemical methods.

Serum Arginine Levels

Killer-immunoglobulin-like receptor (KIR) genotype status determined based on establish methods.

Spots Global Cancer Trial Database for hd il2

Every month we try and update this database with for hd il2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hd il2

Every month we try and update this database with for hd il2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hd il2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.