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Aerosolized Aldesleukin in Treating Patients With Lung Metastases

Primary Purpose

Metastatic Malignant Neoplasm in the Lung, Metastatic Melanoma, Metastatic Osteosarcoma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Aerosolized Aldesleukin

Laboratory Biomarker Analysis

About this trial

This is an interventional treatment trial for Metastatic Malignant Neoplasm in the Lung

Eligibility Criteria

12 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (aerosolized aldesleukin)

Arm Description

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

Outcomes

Primary Outcome Measures

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)

The dose escalation will be conducted via the accelerated titration method for the first 2 dose levels.

Incidence of adverse events (AE)s, using the CTCAE v4.0 (Phase II)

AEs will be summarized by severity according to the worst grade experienced over the number of patients at risk.

Response of measurable lesions to aerosol aldesleukin using modified RECIST (Phase II)

Response analysis will be performed on intent-to-treat, that is, any patient who enrolled into the expansion cohort. Patients who withdraw before the end of 2 months without responding will be considered non-responders. The two-sided 95% Clopper-Pearson confidence intervals will be calculated for the proportion of patients with responses.

Secondary Outcome Measures

IL-2 levels in serum

Serum IL-2 levels will be compared with maximum grade of toxicity to determine whether our hypothesis of "spillover" of IL-2 in the circulation - i.e. some escaping the receptor gauntlet of IL-2 receptor bearing cells in pulmonary lymphatics.

Changes in biomarker levels

Changes in biomarker levels between pre- and post-treatment tissue samples will be assessed using paired t-tests (if the data are normally distributed) or Wilcoxon signed-rank tests (otherwise). Will graph the data using histograms, box plots and dot plots. With 20 patients, using a 2-sided 5% alpha, there would be 80% power to detect an effect size of 0.66 (where the effect size is the mean difference divided by the standard deviation of the differences).

Full Information

NCT ID

NCT01590069

First Posted

April 30, 2012

Last Updated

October 5, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01590069

Brief Title

Aerosolized Aldesleukin in Treating Patients With Lung Metastases

Official Title

Phase I/II Study of Aerosol Interleukin-2 for Pulmonary Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 28, 2012 (Actual)

Primary Completion Date

April 30, 2024 (Anticipated)

Study Completion Date

April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (aerosolized aldesleukin)

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Aerosolized Aldesleukin

Other Intervention Name(s)

Aerosolized Recombinant IL-2

Intervention Description

Breathe aerosolized aldesleukin

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Optional correlative studies

Primary Outcome Measure Information:

Title

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)

Description

The dose escalation will be conducted via the accelerated titration method for the first 2 dose levels.

Time Frame

28 days

Title

Incidence of adverse events (AE)s, using the CTCAE v4.0 (Phase II)

Description

AEs will be summarized by severity according to the worst grade experienced over the number of patients at risk.

Time Frame

Up to 4 years

Title

Response of measurable lesions to aerosol aldesleukin using modified RECIST (Phase II)

Description

Time Frame

Up to 4 years

Secondary Outcome Measure Information:

Title

IL-2 levels in serum

Description

Time Frame

Day 1 of therapy

Title

Changes in biomarker levels

Description

Time Frame

Baseline to 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Najat Daw

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center Website

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Aerosolized Aldesleukin in Treating Patients With Lung Metastases

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