Clinical trial NCT01590069: Aerosolized Aldesleukin in Treating Patients With Lung Metastases
Official title: Phase I/II Study of Aerosol Interleukin-2 for Pulmonary Metastases
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Metastatic Malignant Neoplasm in the Lung
Metastatic Melanoma
Metastatic Osteosarcoma
Metastatic Renal Cell Cancer
Sarcoma
Stage IV Cutaneous Melanoma AJCC v6 and v7
Stage IV Osteosarcoma AJCC v7
Stage IV Renal Cell Cancer AJCC v7
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-05-02
Enrollment: 70
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I/II trial studies the side effects and best dose of aerosolized aldesleukin and to see how well it works in treating patients with cancer that has spread from the original tumor to the lungs. Biological therapies, such as aerosolized aldesleukin, may stimulate or suppress the immune system in different ways and stop tumor cells from growing.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate toxicity in patients with lung metastases during aerosol interleukin (IL)-2 (aldesleukin) therapy using self-report, remote spirometry and pulse oximetry.

SECONDARY OBJECTIVES:

I. To determine dose and schedule of an acceptable aerosol IL-2 regimen and correlate with absolute lymphocyte count (ALC).

II. To determine serum IL-2 levels on day 1 of therapy for evidence of spillover into circulation and correlate with absence or presence of toxicity.

III. To evaluate the efficacy of aerosol IL-2 treatment using Response Evaluation Criteria in Solid Tumors (RECIST).

TERTIARY OBJECTIVES:

I. To evaluate the histology in post-surgical specimens in patients who undergo surgery for lung metastases following aerosol IL-2 treatment as an optional procedure.

II. To evaluate immune correlates from optional pre-treatment biopsy and post-surgical specimen.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive aerosolized aldesleukin once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression of unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Eligibility criteria: Inclusion Criteria:

* Patients with diagnosis of advanced cancer with lung metastases; patients with no prior therapy are eligible if there is no known superior alternative medical therapy; for phase Ib expansion cohort diagnosis of osteosarcoma, lung metastases will be required
* Willing to comply with protocol therapy and required safety monitoring (self-report, pulse oximetry, remote spirometry, labs)
* Creatinine =\< 2 x upper limit of normal (ULN)
* Bilirubin =\< 5 x ULN
* Aspartate aminotransferase (AST) =\< 5 x ULN
* Forced vital capacity (FVC) \>= 50% predicted
* Oxygen (O2) saturation at rest \>= 90% (off supplementary oxygen)
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 for ages \>= 16 or Lansky play \>= 80% for ages =\< 15
* Patients must have recovered to =\< grade 1 toxicity (except alopecia and hearing loss) from any prior chemotherapy, other investigational therapy, hormonal, biological, targeted agents
* No radiotherapy within 2 weeks: exception: patients may receive palliative low dose radiotherapy (30 Gy or less) for lesions outside the lung at the discretion of the treating physician; palliative radiotherapy could be given before aerosol treatment is started if necessary
* Subjects have to be able to read and understand English
* Patients with advanced cancer with resectable lung metastases
* Patients with sarcoma, renal cell carcinoma, or melanoma or with known disease outside the lungs and/or thorax

Exclusion Criteria:

* Currently being treated with bronchodilators or corticosteroids
* Females: pregnant or breast feeding and if of child bearing potential (e.g. female of childbearing age that has not been amenorrheic for at least 12 consecutive month or surgically sterilized) not willing to use effective contraception
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bradycardia, related to cardiac disease, bundle branch block, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Subjects with baseline symptoms of fever and/or cough and/or shortness of breath and/or wheezing and/or fatigue grade \>= 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4.0)
* Patients with unresectable lung metastases
* Patients without sarcoma, renal cell carcinoma, or melanoma

Primary outcomes:
measure: Maximum tolerated dose, defined as the highest dose level with six patients with at most one dose limiting toxicity, using the CTCAE v4.0 (Phase I)
timeFrame: 28 days
measure: Incidence of adverse events (AE)s, using the CTCAE v4.0 (Phase II)
timeFrame: Up to 4 years
measure: Response of measurable lesions to aerosol aldesleukin using modified RECIST (Phase II)
timeFrame: Up to 4 years
Secondary outcomes:
measure: IL-2 levels in serum
timeFrame: Day 1 of therapy
measure: Changes in biomarker levels
timeFrame: Baseline to 8 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Najat Daw
role: PRINCIPAL_INVESTIGATOR
References: