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Cisplatin in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer or Lung Metastasis

Phase 1
Completed
Conditions
Metastatic Malignant Neoplasm in the Lung
Stage IIIB Non-Small Cell Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV Adult Soft Tissue Sarcoma
Interventions
Other: Pharmacological Study
Registration Number
NCT01014598
Lead Sponsor
Roswell Park Cancer Institute
Brief Summary

This phase I trial studies the side effects and best dose of cisplatin in treating patients with stage IIIB-IV non-small cell lung cancer or tumors that have spread from where they started to the lung (metastasis). Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cisplatin directly into the arteries around the tumor may kill more tumor cells and cause less damage to normal tissue.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and dose-limiting toxicities of cisplatin when delivered selectively by isolated lung suffusion to patients with any biopsy or cytologically proven resectable or unresectable primary or secondary malignancy in the lung.

SECONDARY OBJECTIVES:

I. To assess lung tissue levels of cisplatin after isolated lung suffusion as a function of the dose delivered.

II. To evaluate systemic and pulmonary artery concentrations of cisplatin during isolated lung suffusion.

OUTLINE: This is a dose-escalation study.

Patients receive cisplatin intra-arterially via isolated lung suffusion over 2 hours. Beginning approximately 2 weeks later (6-8 weeks if indicated for patients with sarcoma undergoing surgery after cisplatin), patients receive standard chemotherapy regimen.

After completion of study treatment, patients are followed up for at least 90 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
Inclusion Criteria
  • Any biopsy or cytologically proven resectable or unresectable primary or secondary (metastatic) malignancy in the lung; this is defined as

    • Tumors whose only remaining residual deposits are confined to the lungs OR
    • Oligometastatic tumors with > 80% of measurable tumor volume in the target lung In both of the above situations, no clinical evidence of central nervous system (CNS) metastases can exist; oligometastatic disease is difficult to define but would, as a guideline, have only 1-4 loci of disease established in 1-2 organ systems outside the affected lung; exceptions to these guidelines can occur, particularly in cases where sites of metastatic disease are equivocal or so minute that it would not exceed 20% of tumor volume
  • Unresectable stage IV non-small cell lung cancer (NSCLC)

  • Unresectable stage IIIB NSCLC

  • Resectable metastatic sarcoma to lung (thoracoscopically resectable)

  • Other malignancies that meet the criteria

  • Eastern Cooperative Oncology Group performance status 0-1

  • No oxygen needs (oxygen use per standard established criteria for oxygen requirements)

  • Modified Borg dyspnea scale < 5

  • Six minute walk >= 50% of the expected distance; this will not be used as exclusion criteria if due to a reason other than respiratory per judgment of physician e.g., pain

  • Ambulatory and resting oxygen (O2) saturation > 88%

  • PPO (predicted post operative)* forced expiratory volume in one second (FEV1) >= 50% predicted

    • PPO values should be calculated for each patient
  • PPO * diffusing capacity of the lung for carbon monoxide (DLCO) >= 50% predicted

    • PPO values should be calculated for each patient
  • PPO * vital capacity >= 50% predicted

    • PPO values should be calculated for each patient
  • Granulocytes > 1,500 ul

  • Platelets >= 100,000 ul

  • Patients must sign a study-specific consent form prior to registration

  • Tumor anatomy must allow the isolated lung suffusion in the judgment of the principal investigator (PI)

Exclusion Criteria
  • Uncontrolled intercurrent disease
  • Prior chemotherapy for proven metastatic disease within 4 weeks
  • Evidence of pulmonary toxicity from previous or ongoing chemotherapy
  • Creatinine > 1.5 mg/dL
  • Liver enzymes > 2 times upper normal
  • Uncontrolled congestive heart failure (in judgment of the PI)
  • Optional: ejection fraction < 40% for clinical evidence of insufficient cardiac reserve (multi gated acquisition scan [MUGA] or echocardiogram [ECHO] will be done only if indicated in the judgment of the PI)
  • Myocardial infarction or angina within past 6 months
  • Contraindications to anticoagulation
  • Hydration intolerance (e.g., uncontrolled congestive heart failure [CHF])
  • Human immunodeficiency virus positive (HIV+) on antiretroviral therapy
  • Pregnant or lactating
  • Diffuse pulmonary fibrosis involving over 25% of the total lung parenchyma
  • Previous radiation for thorax
  • Metastatic sarcoma to lung that is not able to have tumors resected thoracoscopically
  • Prior lung removal in the affected lung (would have decreased lung volume)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (cisplatin)Pharmacological StudyPatients receive cisplatin intra-arterially via isolated lung suffusion over 2 hours. Beginning approximately 2 weeks later (6-8 weeks if indicated for patients with sarcoma undergoing surgery after cisplatin), patients receive standard chemotherapy regimen.
Treatment (cisplatin)CisplatinPatients receive cisplatin intra-arterially via isolated lung suffusion over 2 hours. Beginning approximately 2 weeks later (6-8 weeks if indicated for patients with sarcoma undergoing surgery after cisplatin), patients receive standard chemotherapy regimen.
Primary Outcome Measures
NameTimeMethod
Acute toxicity assessed using CTCAE version 4.0Within 7 days from lung infusion
Frequency of patients experiencing dose limiting toxicities (DLT) as well as non-DLTWithin 30 days of the procedure

DLT is defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A grade 3 or above adverse event shall be considered a DLT in this study if attributed to the isolated lung suffusion cisplatin dose.

Reversibility of all toxicities from this approach.Up to 90 days from the start of lung infusion therapy
Secondary Outcome Measures
NameTimeMethod
Lung, systemic, and pulmonary artery concentrations of cisplatinBefore pulmonary artery release, at 15 minutes, and 1 hour

Analysis of variance models with appropriate transformations of the variables, or nonparametric tests such as the Kruskal-Wallis test will be used as appropriate.

Pulmonary function test with diffusion capacityUp to 30 days post-treatment

Will be summarized with respect to the percentage of cisplatin given directly to the lung. Analysis of variance models with appropriate transformations of the variables, or nonparametric tests such as the Kruskal-Wallis test will be used as appropriate.

Split lung function testUp to 30 days post-treatment

Will be summarized with respect to the percentage of cisplatin given directly to the lung. Analysis of variance models with appropriate transformations of the variables, or nonparametric tests such as the Kruskal-Wallis test will be used as appropriate.

Trial Locations

Locations (1)

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
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