Clinical trial NCT00554515: The High-Dose Aldesleukin (IL-2) "Select" Trial for Patients With Metastatic Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Kidney
Renal Cell
Metastatic
interleukin-2
select
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: City of Hope National Medical Center
name: Providence Cancer Center, Earle A. Chiles Research Institute
name: Dartmouth-Hitchcock Medical Center
name: Indiana University
name: Loyola University
name: Our Lady of Mercy Medical Center
name: Roswell Park Cancer Institute
name: University of California, Los Angeles
name: University of Cincinnati
name: University of Pittsburgh
name: University of Virginia
name: Vanderbilt University
name: Wayne State University
name: Dana-Farber Cancer Institute
First posted: 2007-11-07
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Objective Response in ISM Good Risk Group
timeFrame: 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 outcomes:
measure: Objective Response Rate in ISM Poor Risk Group
timeFrame: 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).
measure: Objective Response Rate (Independent Assessment)
timeFrame: 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).
measure: Overall Survival
timeFrame: Participants were followed for survival up to 7 years.
measure: 3-Year Progression-Free Survival Rate
timeFrame: 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.
measure: Objective Response Rate by MSKCC Risk Group
timeFrame: 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).
measure: Objective Response Rate by UCLA SANI Score
timeFrame: 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).
measure: Objective Response Rate by Tumor Type
timeFrame: 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).
measure: Objective Response Rate by Clear Cell Histology Risk Group
timeFrame: 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.
measure: Objective Response Rate by CA-9 Score (CAIX Classification)
timeFrame: 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).
measure: Objective Response Rate by PD-L1 Tumor
timeFrame: 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).
measure: Objective Response Rate by B7-H3 Tumor
timeFrame: 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).
measure: Objective Response Rate by CA-9 SNP
timeFrame: 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).
measure: Progression-Free Survival
timeFrame: 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 outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: David F McDermott, MD
role: STUDY_CHAIR
affiliation: City of Hope National Medical Center
name: Kim Margolin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chiles Cancer Center
name: Walter Urba, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Marc Ernstoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Theodore Logan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola University
name: Joseph Clark, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Our Lady of Mercy Cancer Center
name: Janice Dutcher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Roswell Park Cancer Institute
name: Michael Wong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Allen Pantuck, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: Leslie Oleksowicz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Leonard Appleman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Geoffrey Weiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Jeffrey Sosman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Ulka Vaishampayan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.