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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: HD IL2

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically confirmed renal cell carcinoma that is metastatic or unresectable.
• If patients have measurable disease restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
• Patients must provide access to tissue blocks containing adequate tumor for interpretation and analysis.
• Patients must have measurable disease.
• Patients must have good performance status (ECOG 0 or 1; Karnofsky PS 100-80%).
• Patients must have adequate organ function.
• Patients must have no contraindication of vasopressor agents.
• Patients must be ≥ 18 years of age.

Exclusion Criteria:

• Patients who have received systemic therapy for metastatic disease.
• Patients with organ allografts.
• Patients who require or are likely to require systemic corticosteroid therapy for intercurrent illness.
• Patients with any significant medical disease other than the malignancy (e.g. COPD, patients with ascites or pleural effusions), which in the opinion of the investigator would significantly increase the risk of immunotherapy.
• Patients with a history of another malignancy within the past 5 years other than surgically cured non-melanoma skin cancer, carcinoma-in-situ or Stage I carcinoma of the cervix.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HD IL2; 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.

Drug: HD IL2; Other Names: Proleukin; Aldesleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response in ISM Good Risk Group	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate in ISM Poor Risk Group	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate (Independent Assessment)	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Overall Survival	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.	Participants were followed for survival up to 7 years.
3-Year Progression-Free Survival Rate	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Relevant for this endpoint was disease status at 3 y.
Objective Response Rate by MSKCC Risk Group	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by UCLA SANI Score	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by Tumor Type	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by Clear Cell Histology Risk Group	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Response status was confirmed by an independent assessment of radiographs. Participants received up to 3 courses of 12 weeks duration each.
Objective Response Rate by CA-9 Score (CAIX Classification)	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by PD-L1 Tumor	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by B7-H3 Tumor	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Objective Response Rate by CA-9 SNP	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Progression-Free Survival	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.	Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Median survival follow-up was X months (95% CI: ).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
VHL Genotype Status	VHL genotype status will be determined based on establish methods.	Determined from baseline sample.

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: University of California, Los Angeles; Dana-Farber Cancer Institute; Wayne State University; University of Pittsburgh; Vanderbilt University; Dartmouth-Hitchcock Medical Center; Roswell Park Cancer Institute; University of Virginia; Indiana University; University of Cincinnati; Loyola University; City of Hope National Medical Center; Providence Cancer Center, Earle A. Chiles Research Institute; Our Lady of Mercy Medical Center
• Investigators: Study Chair: David F McDermott, MD, Beth Israel Deaconess Medical Center; Principal Investigator: Kim Margolin, MD, City of Hope National Medical Center; Principal Investigator: Walter Urba, MD, Chiles Cancer Center; Principal Investigator: Marc Ernstoff, MD, Dartmouth-Hitchcock Medical Center; Principal Investigator: Theodore Logan, MD, Indiana University; Principal Investigator: Joseph Clark, MD, Loyola University; Principal Investigator: Janice Dutcher, MD, Our Lady of Mercy Cancer Center; Principal Investigator: Michael Wong, MD, Roswell Park Cancer Institute; Principal Investigator: Allen Pantuck, MD, University of California, Los Angeles; Principal Investigator: Leslie Oleksowicz, MD, University of Cincinnati; Principal Investigator: Leonard Appleman, MD, University of Pittsburgh; Principal Investigator: Geoffrey Weiss, MD, University of Virginia; Principal Investigator: Jeffrey Sosman, MD, Vanderbilt University; Principal Investigator: Ulka Vaishampayan, MD, Wayne State University

Publications and helpful links

General Publications

• McDermott DF. Update on the application of interleukin-2 in the treatment of renal cell carcinoma. Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):716s-720s. doi: 10.1158/1078-0432.CCR-06-1872.
• Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A, Febbo P, Upton M, Lechpammer M, Signoretti S. Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res. 2005 May 15;11(10):3714-21. doi: 10.1158/1078-0432.CCR-04-2019.
• McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI, Sosman JA, Dutcher JP, Logan TF, Curti BD, Ernstoff MS, Appleman L, Wong MK, Khushalani NI, Oleksowicz L, Vaishampayan UN, Mier JW, Panka DJ, Bhatt RS, Bailey AS, Leibovich BC, Kwon ED, Kabbinavar FF, Belldegrun AS, Figlin RA, Pantuck AJ, Regan MM, Atkins MB. The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015 Feb 1;21(3):561-8. doi: 10.1158/1078-0432.CCR-14-1520. Epub 2014 Nov 25.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): October 31, 2013
• Study Completion (Actual): October 31, 2013

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (Estimated): November 7, 2007

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic; interleukin-2; Kidney; Renal Cell; select
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: DFHCC 06-149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No