Clinical trial NCT01160445
Conditions: Metastatic Melanoma Metastatic Renal Cancer
Keywords: Metastatic Melanoma Metastatic Kidney Cancer Clinical Performance Tumor Regression Toxicity
Sponsor: National Cancer Institute (NCI)
Start date: 2010-06-01; Completion date: 2012-01-01
Enrollment: 9 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Background:

* Aldesleukin (IL-2) is a drug that can help to shrink tumors in some patients with metastatic renal cancer and metastatic melanoma. It is possible that removing certain white blood cells (known as CD4 cells) before IL-2 treatment may improve the treatment effects.
* Zanolimumab is an antibody that works by destroying CD4 cells in the blood. Researchers are interested in determining whether zanolimumab can improve the results of IL-2 treatment if it is given before, during, and after IL-2 treatment. In addition, further research with zanolimumab may provide more information on how IL-2 treatment causes tumors to stop growing or shrink.

Objectives:

\- To evaluate the effectiveness of IL-2 treatment in conjunction with zanolimumab in individuals with metastatic cancer.

Eligibility:

\- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma or metastatic kidney cancer.

Design:

* Eligible participants will be screened with a full physical examination and medical history, imaging studies, and blood samples, including leukapheresis, to remove a sample of white blood cells for testing purposes. Participants may also have a colonoscopy and biopsies if they have received previous treatments that have been known to cause colon damage.
* Participants will be treated with zanolimumab and IL-2 treatment for 9 weeks.
* Zanolimumab will be given on an outpatient basis during weeks 1 through 4, 6, 8, and 9. In weeks 5 and 7, participants will receive zanolimumab as an inpatient in addition to IL-2 therapy.
* Inpatient IL-2 treatment will be given during weeks 5 and 7. Up to 15 doses of IL-2 treatment will be given over a maximum of 5 days, followed by inpatient recovery time.
* During week 5, participants will have tumor imaging studies prior to receiving zanolimumab and IL-2 treatment.
* About 2 weeks after the treatment period, participants will return to the clinical center for a 2-day evaluation with a physical examination, imaging studies, and blood samples.
* Participants whose tumors have responded to treatment will be offered up to two additional courses of treatment, starting 6 to 8 weeks after the last IL-2 dose. Subsequent courses will be given exactly as described above in the initial course of treatment. Participants whose tumors do not respond to treatment will have follow-up evaluations as required by the study researchers.

Detailed description:
Background:

Zanolimumab is a human monoclonal antibody (mAb) that specifically recognizes CD4 protein expressed on a subset of T lymphocytes and on monocytes from humans, and non-human primates.

Ongoing clinical studies have identified a 14 mg/kg dose of zanolimumab weekly as a safe and efficacious dose. Toxicities of zanolimumab included headache, influenza-like illness, injection/infusion site reaction, nasopharyngitis, pyrexia, diarrhea, fatigue, and cytokine release syndrome at the time of infusion.

The current protocol is based on the hypothesis that transient elimination of CD4+ T-regulatory cells with zanolimumab will enhance the clinical effectiveness of aldesleukin (IL-2) administration by decreasing T-regulatory cell generation.

Objectives:

Primary objective:

Determine the ability of a combination of aldesleukin and zanolimumab (anti-CD4 mAb) administration to mediate tumor regression in patients with metastatic melanoma and metastatic kidney cancer.

Secondary objectives:

Determine the rate of depletion and repopulation of CD4+ cells.

Determine the toxicity of this treatment.

Determine the potential for pharmacokinetic interaction between zanolimumab and aldesleukin.

Eligibility:

Patients who are 18 years of age or older must have:

measurable metastatic melanoma or metastatic kidney cancer;

clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, or 1.

Patients may not have:

previously received high dose aldesleukin.

Design:

Patients will receive zanolimumab at a dose of 14 mg/kg as an intravenous (i.v.) infusion weekly for 9 weeks. After the fifth and seventh dose of zanolimumab, aldesleukin will administered as an i.v. bolus at a dose of 720,000 IU/kg every 8 hours for a maximum of 15 doses.

Patients will undergo complete evaluation of tumor with physical examination, computed tomography (CT) and clinical laboratory evaluation 2 weeks after zanolimumab administration. If the patient has stable disease (SD) or tumor shrinkage, repeat complete evaluations will be performed every 1-3 months. After the first year, patients continuing to respond will be followed with this evaluation every 3-4 months until off study criteria are met.

If patients have stable disease or a partial response to treatment after the initial evaluation, or if a patient recurs or progresses after a clinical response, they may be eligible for re-treatment.

Patients will be entered into one of two strata: metastatic melanoma or metastatic renal cancer. Each of the strata will be conducted using an optimal two-stage phase II design to rule out an unacceptably low 15% clinical response rate, in favor of a modestly high response rate of 35% (p1=0.35).

Arms: arm 1: Patients with metastatic melanoma Zanolimumab 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.

Aldesleukin (IL-2) 720,000 IU/kg every 8 hours for a maximum of 15 doses. arm 2: Patients with metastatic renal cancer Zanolimumab 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.

Aldesleukin (IL-2) 720,000 IU/kg every 8 hours for a maximum of 15 doses.
Interventions: intervention 1: Zanolimumab intervention 2: Aldesleukin
Intervention descriptions: intervention 1: 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks. intervention 2: 720,000 IU/kg every 8 hours for a maximum of 15 doses.

Protocol documents: