Kidney CancerPhase 2NCT00100906
Sequential ATRA Then IL-2 for Modulation of Dendritic Cells and Treatment of Metastatic Renal Cell Cancer
A Phase 2 study testing IL-2 and ATRA in people with Kidney Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
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. 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?
- IL-2 and ATRA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Jul 2013
- Phase
- Phase 2
- 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:
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612-9497
About this study
Official title: 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.
Read the 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.
- Conditions
- Kidney Cancer
- Being tested
- IL-2, ATRA
- Keywords
- stage IV renal cell cancer, recurrent 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.
IL-2Drug
Also called interleukin-2, aldesleukin, Proleukin™, Recombinant Human Interleukin-2
Immunotherapy with interleukin-2
ATRADrug
Also called tretinoin, Vesanoid™, all-trans retinoic acid
| Study group | Role | What they receive |
|---|---|---|
| ATRA Followed by IL-2 - Dose Level A | Active comparator | 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. Receives: Drug: IL-2; Drug: ATRA |
| ATRA Followed by IL-2 - Dose Level B | Active comparator | 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. Receives: Drug: IL-2; Drug: ATRA |
| ATRA Followed by IL-2 - Level C | Active comparator | 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. Receives: Drug: IL-2; Drug: ATRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of Dendritic Cells (DC) to Circulating Immature Cells (ImC) Before and After Treatment
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.
Measured: 1 year, 3 months
Secondary outcomes (2)
Frequency of Treatment-Related Side Effects
Review of adverse events utilizing Common Toxicity Criteria (CTC) V3.
Measured: 1 year, 3 months
Overall Response Rate (ORR)
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.
Measured: 1 year, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2005 (estimated)
- Study startAug 2004
- Primary completionJun 2006
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institutes of Health (NIH), Chiron Corporation
- Responsible party
- Sponsor
- Investigators
- Mayer Fishman, M.D., Ph.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00100906
- Sponsor's protocol ID
- MCC-13920
- Other IDs
- CA101324, CA84488
- Status last verified
- Jul 2013
- First submitted
- 6 Jan 2005
- Last updated
- 16 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, Lush RM, Antonia S, Gabrilovich DI. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006 Sep 15;66(18):9299-307. doi: 10.1158/0008-5472.CAN-06-1690.
PubMed 16982775
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer
- ClinicalTrials.gov ID
- NCT00100906
- Acronym / sponsor ID
- MCC-13920
- Conditions
- Kidney Cancer
- Keywords
- stage IV renal cell cancer, recurrent renal cell cancer, clear cell renal cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institutes of Health (NIH), Chiron Corporation
- Study start
- Aug 2004
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 7 Jan 2005 (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: 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ATRA Followed by IL-2 - Dose Level A | Active comparator | Drug: IL-2, Drug: ATRAPatients 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. |
| ATRA Followed by IL-2 - Dose Level B | Active comparator | Drug: IL-2, Drug: ATRAPatients 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. |
| ATRA Followed by IL-2 - Level C | Active comparator | Drug: IL-2, Drug: ATRAPatients 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. |
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 |
|---|---|---|
| IL-2Also: interleukin-2, aldesleukin, Proleukin™, Recombinant Human Interleukin-2Immunotherapy with interleukin-2 | Drug | ATRA Followed by IL-2 - Dose Level A, ATRA Followed by IL-2 - Dose Level B, ATRA Followed by IL-2 - Level C |
| ATRAAlso: tretinoin, Vesanoid™, all-trans retinoic acid | Drug | ATRA Followed by IL-2 - Dose Level A, ATRA Followed by IL-2 - Dose Level B, ATRA Followed by IL-2 - Level C |
Primary outcome
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.
2 secondary outcomes
Frequency of Treatment-Related Side Effects
Time frame: 1 year, 3 months
Overall Response Rate (ORR)
Time frame: 1 year, 3 months
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 16 Aug 2013.
- Results publication: PubMed 16982775Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, Lush RM, Antonia S, Gabrilovich DI. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006 Sep 15;66(18):9299-307. doi: 10.1158/0008-5472.CAN-06-1690.
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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.
Mayer Fishman, M.D., Ph.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IL-2 and ATRA in people with Kidney Cancer, run by H. Lee Moffitt Cancer Center and Research Institute 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 16 Aug 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Ratio of Dendritic Cells (DC) to Circulating Immature Cells (ImC) Before and After Treatment (time frame: 1 year, 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00100906, which also lists 1 linked publication.
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 16 Aug 2013.