- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00100906
Sequential ATRA Then IL-2 for Modulation of Dendritic Cells and Treatment of Metastatic Renal Cell Cancer
Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer
RATIONALE: Tretinoin may help cells that are involved in the body's immune response to work better. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving tretinoin together with interleukin-2 may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying how well giving three different doses of tretinoin together with interleukin-2 works in treating patients with stage IV kidney cancer.
Study Overview
Detailed Description
OBJECTIVES:
Primary
- Determine the ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment with 3 different doses of tretinoin in patients with stage IV renal cell cancer.
- Assess in vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment with tretinoin and interleukin-2 in these patients.
Secondary
- Determine the frequency of treatment-related side effects in these patients.
- Determine clinical objective response and progression-free survival of patients treated with this regimen.
- Correlate DC:ImC ratio with clinical objective response in patients treated with this regimen.
- Correlate the extent of change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels in these patients.
OUTLINE: This is a randomized, open-label study. Specimens are stratified according to patient prognostic factors, tumor bulk, and extent of dendritic cell to circulating immature cell ratio derangement. Patients are randomized to 1 of 3 tretinoin doses.
Patients are followed for up to 2 years.
PROJECTED ACCRUAL: A total of 27-36 patients (9-12 per treatment arm) will be accrued for this study within 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612-9497
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed renal cell cancer
- Stage IV disease
- Histology with clear cell component
- Metastatic OR incompletely resected disease
- Non-measurable disease allowed
Underwent complete or partial nephrectomy more than 90 days ago
- No unresected primary cancer
No more than 2 of the following adverse factors:
- Hemoglobin < 10.0 g/dL
- Corrected calcium > upper limit of normal (ULN)
- Lactic dehydrogenase > 1.5 times ULN
- Eastern Cooperative Oncology Group (ECOG) performance status 2
- Brain metastasis allowed provided more than 90 days of clinical and radiologic stability after the end of its active treatment
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- See Disease Characteristics
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- See Disease Characteristics
- Serum glutamic oxaloacetic transaminase (SGOT) < 3 times normal
- Bilirubin < 2 times normal
Renal
- See Disease Characteristics
- Creatinine clearance > 40 mL/min
Cardiovascular
None of the following cardiovascular conditions within the past year:
- Uncontrolled hypertension
- Myocardial infarction
- Unstable angina
- New York Heart Association class II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Class II-IV peripheral vascular disease within the past year
- Other clinically significant cardiovascular disease
Immunologic
- No history of immunodeficiency disease
- No HIV infection
- No ongoing serious infection
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use two methods of effective contraception during and for 1 month (for women) or 6 months (for men) after study treatment
- Other prior malignancy allowed provided there is no evidence of active disease
- No other medical contraindication to tretinoin or interleukin-2
- No serious non-healing wound, ulcer, or bone fracture
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 60 days since prior immunotherapy
Chemotherapy
- At least 60 days since prior cytotoxic chemotherapy
Endocrine therapy
- See Radiotherapy
- No prior corticosteroids at > physiologic replacement doses for > 3 days within the past 90 days
- Concurrent tamoxifen, toremifene, megestrol, or gonadotropin-releasing hormone agonists allowed
- Concurrent inhaled steroids allowed
Radiotherapy
More than 7 days since prior external-beam radiotherapy
- No steroid requirement during radiotherapy
Surgery
- See Disease Characteristics
- At least 30 days since other prior debulking surgery
Other
- Prior adjuvant therapy for resected, synchronous stage IV disease allowed
Prior adjuvant therapy allowed
- Study therapy is not to be used as adjuvant therapy for completely resected late (> 1 year until identification) solitary site of disease metastasis or non-metastatic disease
- No prior participation in this clinical study
- At least 60 days since other prior anticancer drugs
- Concurrent seizure medication allowed
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: ATRA Followed by IL-2 - Dose Level A
Patients were assigned to one of three ATRA dose levels, at a 1:1:1 ratio, using a randomly permuted list assignments, with the assignment generally being made on the initial day of treatment. Week 1: One dose daily of IL-2 for 5 days followed by 2 days off. Weeks 2-6: One dose daily of IL-2 for 5 days followed by 2 days off. After the IL-2: 2-3 weeks rest, with no treatment. During this time a repeat physical exam, history and X-ray scans will be performed. If there has not been progression (worsening) of the patient's tumor, they will continue to a second 8-week treatment schedule. This schedule will be the same as the first, unless the patients dose had to be reduced. If so, patient's will get that reduced dose. It consists of 1 week of ATRA, 1 week of rest, followed by 6 weeks of IL-2. The same blood tests are collected during that second cycle. |
Immunotherapy with interleukin-2
Other Names:
Other Names:
|
Active Comparator: ATRA Followed by IL-2 - Dose Level B
Patients were assigned to one of three ATRA dose levels, at a 1:1:1 ratio, using a randomly permuted list assignments, with the assignment generally being made on the initial day of treatment. Week 1: One dose daily of IL-2 for 5 days followed by 2 days off. Weeks 2-6: One dose daily of IL-2 for 5 days followed by 2 days off. After the IL-2: 2-3 weeks rest, with no treatment. During this time a repeat physical exam, history and X-ray scans will be performed. If there has not been progression (worsening) of the patient's tumor, they will continue to a second 8-week treatment schedule. This schedule will be the same as the first, unless the patients dose had to be reduced. If so, patient's will get that reduced dose. It consists of 1 week of ATRA, 1 week of rest, followed by 6 weeks of IL-2. The same blood tests are collected during that second cycle. |
Immunotherapy with interleukin-2
Other Names:
Other Names:
|
Active Comparator: ATRA Followed by IL-2 - Level C
Patients were assigned to one of three ATRA dose levels, at a 1:1:1 ratio, using a randomly permuted list assignments, with the assignment generally being made on the initial day of treatment. Week 1: One dose daily of IL-2 for 5 days followed by 2 days off. Weeks 2-6: One dose daily of IL-2 for 5 days followed by 2 days off. After the IL-2: 2-3 weeks rest, with no treatment. During this time a repeat physical exam, history and X-ray scans will be performed. If there has not been progression (worsening) of the patient's tumor, they will continue to a second 8-week treatment schedule. This schedule will be the same as the first, unless the patients dose had to be reduced. If so, patient's will get that reduced dose. It consists of 1 week of ATRA, 1 week of rest, followed by 6 weeks of IL-2. The same blood tests are collected during that second cycle. |
Immunotherapy with interleukin-2
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ratio of Dendritic Cells (DC) to Circulating Immature Cells (ImC) Before and After Treatment
Time Frame: 1 year, 3 months
|
Determine the ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment with 3 different doses of tretinoin in patients with stage IV renal cell cancer.
|
1 year, 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of Treatment-Related Side Effects
Time Frame: 1 year, 3 months
|
Review of adverse events utilizing Common Toxicity Criteria (CTC) V3.
|
1 year, 3 months
|
Overall Response Rate (ORR)
Time Frame: 1 year, 3 months
|
Objective Response Rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Evaluate per-patient observed best clinical responses, after 11-12 weeks of treatment.
|
1 year, 3 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Mayer Fishman, M.D., Ph.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antineoplastic Agents
- Dermatologic Agents
- Keratolytic Agents
- Aldesleukin
- Tretinoin
- Interleukin-2
Other Study ID Numbers
- MCC-13920
- CA101324 (Other Grant/Funding Number: NIH)
- CA84488 (Other Grant/Funding Number: NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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