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

This study has been completed.
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
David F. McDermott, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00554515
First received: November 6, 2007
Last updated: April 13, 2017
Last verified: April 2017
  Purpose

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.


Condition Intervention Phase
Metastatic Renal Cell Carcinoma Drug: HD IL2 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by David F. McDermott, MD, Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Objective Response in ISM Good Risk Group [ Time Frame: 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). ]
    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.


Secondary Outcome Measures:
  • Objective Response Rate in ISM Poor Risk Group [ Time Frame: 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). ]
    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.

  • Objective Response Rate (Independent Assessment) [ Time Frame: 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). ]
    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 [ Time Frame: Participants were followed for survival up to 7 years. ]
    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 [ Time Frame: 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. ]
    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.

  • Objective Response Rate by MSKCC Risk Group [ Time Frame: 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). ]
    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.

  • Objective Response Rate by UCLA SANI Score [ Time Frame: 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). ]
    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.

  • Objective Response Rate by Tumor Type [ Time Frame: 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). ]
    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.

  • Objective Response Rate by Clear Cell Histology Risk Group [ Time Frame: 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. ]
    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.

  • Objective Response Rate by CA-9 Score (CAIX Classification) [ Time Frame: 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). ]
    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.

  • Objective Response Rate by PD-L1 Tumor [ Time Frame: 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). ]
    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.

  • Objective Response Rate by B7-H3 Tumor [ Time Frame: 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). ]
    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.

  • Objective Response Rate by CA-9 SNP [ Time Frame: 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). ]
    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.

  • Progression-Free Survival [ Time Frame: 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: ). ]
    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.

  • VHL Genotype Status [ Time Frame: Determined from baseline sample. ]
    VHL genotype status will be determined based on establish methods.

  • KIR Genotype Status [ Time Frame: Determined from baseline sample. ]
    Killer-immunoglobulin-like receptor (KIR) genotype status determined based on establish methods.

  • Serum Arginine Levels [ Time Frame: Determined from baseline sample. ]
    Serum arginine levels will be determined based on establish immunohistochemical methods.


Enrollment: 123
Study Start Date: November 2006
Study Completion Date: October 31, 2013
Primary Completion Date: October 31, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554515

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
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
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
  More Information

Publications:
Responsible Party: David F. McDermott, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00554515     History of Changes
Obsolete Identifiers: NCT00536757
Other Study ID Numbers: DFHCC 06-149
Study First Received: November 6, 2007
Results First Received: April 13, 2017
Last Updated: April 13, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David F. McDermott, MD, Beth Israel Deaconess Medical Center:
Kidney
Renal Cell
Metastatic
interleukin-2
select

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017