Kidney CancerEarly Phase 1NCT00278369
Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
A Early Phase 1 study testing aldesleukin and denileukin diftitox in people with Kidney Cancer, run by Northwestern University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer
- What is being tested?
- aldesleukin and denileukin diftitox
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Sep 2010
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
About this study
Official title: A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma
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.
Read the detailed 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.
- Conditions
- Kidney Cancer
- Being tested
- aldesleukin, denileukin diftitox
- Keywords
- recurrent renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldesleukinBiological
Also called IL-2, Interleukin-2, Proleukin
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 diftitoxBiological
Also called ONTAK (denileukin diftitox), DAB 389 IL-2
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course Receives: 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 Receives: 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 Receives: Biological: aldesleukin; Biological: denileukin diftitox |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to assess for toxicity
To assess the toxicity
Measured: 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
To investigate differences in peak and duration.
Measured: 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
To investigate the effects of denileukin diftitox
Measured: 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.
To perform TGF-beta promoter and TGF-beta receptor genotyping
Measured: 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
Overall response rate will be assessed.
Measured: CT scans and other pertinent studies will be performed at week 10 to assess response.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2006 (estimated)
- Study startApr 2005
- Primary completionJun 2009
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Timothy Kuzel, Northwestern University
- Investigators
- Timothy M. Kuzel, MD, Study chair, Robert H. Lurie Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00278369
- Sponsor's protocol ID
- NU 04U1
- Other IDs
- P30CA060553, NU-04U1, STU00006770
- Status last verified
- May 2013
- First submitted
- 16 Jan 2006
- Last updated
- 22 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00278369
- Acronym / sponsor ID
- NU 04U1
- Conditions
- Kidney Cancer
- Keywords
- recurrent renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 18 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Biological: aldesleukin, Biological: denileukin diftitox6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course |
| B | Experimental | Biological: aldesleukin, Biological: denileukin diftitox9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course |
| C | Experimental | Biological: aldesleukin, Biological: denileukin diftitox9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aldesleukinAlso: IL-2, Interleukin-2, ProleukinThe 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 | Biological | A, B, C |
| denileukin diftitoxAlso: ONTAK (denileukin diftitox), DAB 389 IL-2Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days. | Biological | A, B, C |
Primary outcome
The primary objective is to assess for toxicity
Time frame: After each cycle of therapy and 30 days after the last treatment.
To assess the toxicity
4 secondary outcomes
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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: CT scans and other pertinent studies will be performed at week 10 to assess response.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy M. Kuzel, MD study chair
Robert H. Lurie Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing aldesleukin and denileukin diftitox in people with Kidney Cancer, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to assess for toxicity (time frame: After each cycle of therapy and 30 days after the last treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2013.