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


Phase 0
18 Years
N/A
Not Enrolling
Both
Kidney Cancer

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

The primary objective is to assess for toxicity

Outcome Description:

To assess the toxicity

Outcome Time Frame:

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

Safety Issue:

Yes

Principal Investigator

Timothy M. Kuzel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NU 04U1

NCT ID:

NCT00278369

Start Date:

April 2005

Completion Date:

September 2010

Related Keywords:

  • Kidney Cancer
  • recurrent renal cell cancer
  • stage IV renal cell cancer
  • clear cell renal cell carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611