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

NCT00100906 | Completed Phase 2

• 3 other identifiers: MCC-13920CA101324CA84488
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Frequency of Treatment-Related Side Effects

  1 year, 3 months

• Overall Response Rate (ORR)

  1 year, 3 months

Study Arms (3)

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.

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.

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.

Drug: IL-2; Drug: ATRA

Interventions

IL-2 DRUG

Immunotherapy with interleukin-2

Also known as: interleukin-2, aldesleukin, Proleukin™, Recombinant Human Interleukin-2

ATRA Followed by IL-2 - Dose Level A; ATRA Followed by IL-2 - Dose Level B; ATRA Followed by IL-2 - Level C

ATRA DRUG

Also known as: tretinoin, Vesanoid™, all-trans retinoic acid

ATRA Followed by IL-2 - Dose Level A; ATRA Followed by IL-2 - Dose Level B; ATRA Followed by IL-2 - Level C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator
• Chiron Corporation: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9497, United States

Location

Related 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. doi: 10.1158/0008-5472.CAN-06-1690.

  PMID: 16982775 RESULT

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

Interleukin-2; aldesleukin; Tretinoin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological

Study Officials

• Mayer Fishman, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2005
• First Posted: January 7, 2005
• Study Start: August 1, 2004
• Primary Completion: June 1, 2006
• Study Completion: July 1, 2013
• Last Updated: August 16, 2013

Record last verified: 2013-07

Locations

US (1)