Clinical trial NCT00100906: Sequential ATRA Then IL-2 for Modulation of Dendritic Cells and Treatment of Metastatic Renal Cell Cancer
Official title: Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: stage IV renal cell cancer
recurrent renal cell cancer
clear cell renal cell carcinoma
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
name: Chiron Corporation
First posted: 2005-01-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Ratio of Dendritic Cells (DC) to Circulating Immature Cells (ImC) Before and After Treatment
timeFrame: 1 year, 3 months
Secondary outcomes:
measure: Frequency of Treatment-Related Side Effects
timeFrame: 1 year, 3 months
measure: Overall Response Rate (ORR)
timeFrame: 1 year, 3 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Mayer Fishman, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.