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

This study has been completed.
Sponsor:
Collaborators:
Chiron Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00100906
First received: January 6, 2005
Last updated: August 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Drug: IL-2
Drug: ATRA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Ratio of Dendritic Cells (DC) to Circulating Immature Cells (ImC) Before and After Treatment [ Time Frame: 1 year, 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Frequency of Treatment-Related Side Effects [ Time Frame: 1 year, 3 months ] [ Designated as safety issue: Yes ]
    Review of adverse events utilizing Common Toxicity Criteria (CTC) V3.

  • Overall Response Rate (ORR) [ Time Frame: 1 year, 3 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 18
Study Start Date: August 2004
Study Completion Date: July 2013
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: IL-2
Immunotherapy with interleukin-2
Other Names:
  • interleukin-2
  • aldesleukin
  • Proleukin™
  • Recombinant Human Interleukin-2
Drug: ATRA
Other Names:
  • tretinoin
  • Vesanoid™
  • all-trans retinoic acid
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.

Drug: IL-2
Immunotherapy with interleukin-2
Other Names:
  • interleukin-2
  • aldesleukin
  • Proleukin™
  • Recombinant Human Interleukin-2
Drug: ATRA
Other Names:
  • tretinoin
  • Vesanoid™
  • all-trans retinoic acid
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.

Drug: IL-2
Immunotherapy with interleukin-2
Other Names:
  • interleukin-2
  • aldesleukin
  • Proleukin™
  • Recombinant Human Interleukin-2
Drug: ATRA
Other Names:
  • tretinoin
  • Vesanoid™
  • all-trans retinoic acid

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00100906

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Chiron Corporation
Investigators
Principal Investigator: Mayer Fishman, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
Publications:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00100906     History of Changes
Other Study ID Numbers: MCC-13920, CA101324, CA84488
Study First Received: January 6, 2005
Last Updated: August 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
stage IV renal cell cancer
recurrent renal cell cancer
clear cell renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Aldesleukin
Interleukin-2
Tretinoin
Analgesics
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Dermatologic Agents
Keratolytic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014