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

Kidney Cancer Clinical Trial

Official title:

Randomized Phase II Trial Of Sequential ATRA Then IL-2 For Modulation Of Dendritic Cells And Treatment Of Metastatic Renal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100906
• Other study ID #: MCC-13920
• Secondary ID: CA101324CA84488
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2005
• Last updated: August 15, 2013
• Start date: August 2004
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2013
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer

Intervention

Drug:
• IL-2
Immunotherapy with interleukin-2
• ATRA

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (4)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Chiron Corporation, National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year, 3 months	No
Secondary	Frequency of Treatment-Related Side Effects	Review of adverse events utilizing Common Toxicity Criteria (CTC) V3.	1 year, 3 months	Yes
Secondary	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.	1 year, 3 months	No