Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer

Kidney Cancer Clinical Trial

Official title:

A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278369
• Other study ID #: NU 04U1
• Secondary ID: P30CA060553NU-04
• Status: Completed
• Phase: Phase 0
• First received: January 16, 2006
• Last updated: May 20, 2013
• Start date: April 2005
• Est. completion date: September 2010

Study information

• Verified date: May 2013
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.

Description:

OBJECTIVES:

Primary

• Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.

Secondary

• Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.

• Determine the overall response rate (partial and complete) in patients treated with this regimen.

• Determine the time to progression in patients treated with this regimen.

OUTLINE: This is a randomized, pilot study.

The first 3 patients enrolled in the study receive high-dose interleukin-2 (IL-2) IV over 15 minutes, 3 times daily, on days 1-5 and 15-19 and denileukin diftitox IV over 15-60 minutes once daily on days 8-10. If no dose-limiting toxicity occurs after receiving denileukin diftitox, subsequent patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes once daily on days -4 to -2 and high-dose IL-2 IV over 15 minutes, 3 times daily, on days 1-5 and 15-19.

• Arm II: Patients receive high-dose IL-2 as in arm I and denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes at a higher dose once daily on days 8-10.

All patients may receive additional treatment with IL-2 alone in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Documented histologically confirmed metastatic renal cell carcinoma

• Clear cell histology

• Disease must be measurable as defined by lesions that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques or > 10 mm with spiral CT scan

• Must have at least one measurable lesion

• If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology

• Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)

• The following are considered nonmeasurable lesions:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast disease

• Lymphangitis cutis/pulmonis

• Cystic lesions

• Abdominal masses not confirmed and followed by imaging techniques

• No CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status < 2

• Life expectancy of at least 4 months

• Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min

• Total bilirubin normal

• Platelets > 100,000/mm³

• WBC > 3,500/mm³

• No evidence of congestive heart failure

• No symptoms of coronary artery disease

• No serious cardiac arrhythmias

• A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms are present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)

• Adequate pulmonary reserve

• Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment

• FEV_1 > 2.0 liters of > 75% predicted for height and age

• Patients unable to perform PFTs will be excluded

• Women who are pregnant or lactating are not eligible

• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study

• Negative pregnancy test

• No known HIV-positive patients

• No evidence of active infection requiring antibiotic therapy

• Must not have a contraindication to treatment with pressor agents

• Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study

• No history of another malignancy within the past 5 years other than basal cell skin cancer

PRIOR CONCURRENT THERAPY:

• Recovered from all toxic effects of prior therapy

• Must not currently receive chronic medication for asthma

• No prior interleukin-2 (IL-2) therapy

• No prior organ allografts

• No systemic corticosteroids in the 4 weeks prior to treatment

• No concurrent systemic steroids

• No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment

• No concurrent radiotherapy, chemotherapy, or other immunotherapy

• No previous investigational agent within 4 weeks prior to the start of study treatment

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Cancer

Intervention

Biological:
• aldesleukin
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment
• denileukin diftitox
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to assess for toxicity	To assess the toxicity	After each cycle of therapy and 30 days after the last treatment.	Yes
Secondary	The secondary objectives are to investigate differences in peak and duration of the expansion of CD4+, CD8+, CD4+CD 25+ and CD56+(dim and bright)CD25+ cells	To investigate differences in peak and duration.	Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.	No
Secondary	To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels	To investigate the effects of denileukin diftitox	Cohort 1: Denileukin diftitox dose of 6µg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9µg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9µg/kg given days 8 and 9.	No
Secondary	To perform TGF-beta promoter and TGF-beta receptor genotyping prior to the start of treatment to search for variants that may be associated with tumor response to therapy.	To perform TGF-beta promoter and TGF-beta receptor genotyping	Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5.	No
Secondary	Overall response rate and time to progression	Overall response rate will be assessed.	CT scans and other pertinent studies will be performed at week 10 to assess response.	No