Sequential ATRA Then IL-2 for Modulation of Dendritic Cells and Treatment of Metastatic Renal Cell Cancer

NCT ID: NCT00100906

Last Updated: 2013-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-08-31

Study Completion Date

2013-07-31

Brief Summary

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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

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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

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Kidney Cancer

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

IL-2

Intervention Type DRUG

Immunotherapy with interleukin-2

ATRA

Intervention Type DRUG

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.

Group Type ACTIVE_COMPARATOR

IL-2

Intervention Type DRUG

Immunotherapy with interleukin-2

ATRA

Intervention Type DRUG

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.

Group Type ACTIVE_COMPARATOR

IL-2

Intervention Type DRUG

Immunotherapy with interleukin-2

ATRA

Intervention Type DRUG

Interventions

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IL-2

Immunotherapy with interleukin-2

Intervention Type DRUG

ATRA

Intervention Type DRUG

Other Intervention Names

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interleukin-2 aldesleukin Proleukin™ Recombinant Human Interleukin-2 tretinoin Vesanoid™ all-trans retinoic acid

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Chiron Corporation

INDUSTRY

Sponsor Role collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mayer Fishman, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

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H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 16982775 (View on PubMed)

Other Identifiers

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CA101324

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CA84488

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MCC-13920

Identifier Type: -

Identifier Source: org_study_id