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

NCT00278369 | Completed Early Phase 1 DMC

• 4 other identifiers: NU 04U1P30CA060553NU-04U1STU00006770
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Cancer

Keywords

recurrent renal cell cancer; stage IV renal cell cancer; clear cell renal cell carcinoma

Outcome Measures

Primary Outcomes (1)

• The primary objective is to assess for toxicity

  To assess the toxicity

  After each cycle of therapy and 30 days after the last treatment.

Secondary Outcomes (4)

• 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

  Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.

• To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels

  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.

• 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.

  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.

• Overall response rate and time to progression

  CT scans and other pertinent studies will be performed at week 10 to assess response.

Study Arms (3)

A

EXPERIMENTAL

6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course

Biological: aldesleukin; Biological: denileukin diftitox

B

EXPERIMENTAL

9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course

Biological: aldesleukin; Biological: denileukin diftitox

C

EXPERIMENTAL

9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course

Biological: aldesleukin; Biological: denileukin diftitox

Interventions

aldesleukin BIOLOGICAL

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

Also known as: IL-2, Interleukin-2, Proleukin

A; B; C

denileukin diftitox BIOLOGICAL

Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

Also known as: ONTAK (denileukin diftitox), DAB 389 IL-2

A; B; C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

aldesleukin; Interleukin-2; denileukin diftitox

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Timothy M. Kuzel, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Timothy Kuzel, MD

Study Record Dates

• First Submitted: January 16, 2006
• First Posted: January 18, 2006
• Study Start: April 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: September 1, 2010
• Last Updated: May 22, 2013

Record last verified: 2013-05

Locations

US (1)