PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-Small Cell Lung Cancer (PAINT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nitin Ohri, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT02073968
First received: February 26, 2014
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This phase II trial studies how well intensity modulated radiation therapy adjusted by positron emission tomography (PET) scanning together with combination chemotherapy works in treating patients with stage II-IV non-small cell lung cancer (NSCLC). Radiation therapy uses high energy x rays to kill tumor cells. In intensity-modulated radiotherapy, multiple beam angles and dozens of beam segments are used to deliver highly conformal radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PET-adjusted IMRT together with combination chemotherapy may kill more tumor cells.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Tumors Metastatic to Brain
Procedure: positron emission tomography
Procedure: computed tomography
Radiation: intensity-modulated radiation therapy
Drug: carboplatin
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PET-Adjusted IMRT for NSCLC Trial (PAINT)

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Metabolic response of all pulmonary lesions and thoracic lymph nodes, defined as having maximum SUV less than 6.0 on post-treatment PET/CT [ Time Frame: Up to 16 weeks after completion of radiation therapy ] [ Designated as safety issue: No ]
    Descriptive statistics of baseline demographic and clinical characteristics will be presented. The demographic and clinical characteristics will be compared between responders and non-responder's using chi-square statistics or Fishers exact test for categorical variable and t-test or Wilcoxon Mann-Whitney U test for continuous variables. Efficacy analysis will be performed using single sample pre-post proportion test.


Secondary Outcome Measures:
  • Locoregional progression-free survival assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: From study registration to date of local or regional disease progression or death, censored at the date of data collection, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.

  • Progression-free survival assessed using the RECIST criteria [ Time Frame: From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables.

  • Overall survival [ Time Frame: From study registration to death, censored at the date of data collection, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for overall survival among the predictor variables.

  • Lung cancer cause-specific survival [ Time Frame: From study registration to death directly from lung cancer, censored at the date of data collection, assessed up to 3 years ] [ Designated as safety issue: No ]
    A patient will be considered to have died from lung cancer if he or she had evidence of disease progression at any site and no direct evidence of other cause of death. Kaplan-Meier survival plots will be produced.

  • Grade >= 2 radiation-induced lung toxicity, scored using Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The safety parameters will be presented as frequency and percentages.

  • Grade >= 3 treatment-related toxicity, scored using CTCAE, v. 4 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The safety parameters will be presented as frequency and percentages.


Estimated Enrollment: 39
Study Start Date: July 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (PET-adjusted IMRT, carboplatin, paclitaxel)

RADIOTHERAPY: Patients undergo PET-adjusted IMRT five days a week for 5 weeks.

CONCURRENT CHEMOTHERAPY: Patients receive carboplatin IV over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy.

CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, ANC > 1500, and platelet count > 100,000, patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Procedure: positron emission tomography
Undergo PET-adjusted IMRT
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Procedure: computed tomography
Undergo PET-adjusted IMRT
Other Name: tomography, computed
Radiation: intensity-modulated radiation therapy
Undergo PET-adjusted IMRT
Other Name: IMRT
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the efficacy (based on post-treatment PET findings) of dose-painted intensity-modulated radiotherapy (IMRT) with concurrent and adjuvant chemotherapy for locally-advanced non-small cell lung cancer (LA-NSCLC).

SECONDARY OBJECTIVES:

I. To estimate the efficacy (based on clinical endpoints including locoregional control [LRC], disease-free survival [DFS], and overall survival [OS]) of dose-painted IMRT with concurrent and adjuvant chemotherapy for LA-NSCLC.

II. To evaluate the safety of dose-painted IMRT with concurrent and adjuvant chemotherapy for LA-NSCLC.

III. To evaluate the utility of post-treatment PET/computed tomography (CT) imaging as a predictor of clinical outcomes following treatment with this novel approach.

IV. To explore, in a preliminary manner, whether metabolomic markers in the blood and urine prior to and during the course of treatment are associated with treatment response, clinical endpoints, and treatment-related adverse events such as radiation pneumonitis.

OUTLINE:

RADIATION THERAPY: Patients undergo PET-adjusted IMRT five days a week for 5 weeks.

CONCURRENT CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 3 hours and paclitaxel IV over 1 hour once weekly for 6 weeks beginning week 1 of thoracic radiotherapy.

CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or less, absolute neutrophil count (ANC) > 1500, and platelet count > 100,000, patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks 12-16 weeks, every 3 months for 2 years and then every 6 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically proven (either histologic or cytologic) diagnosis of NSCLC with any of the following stages (according to the American Joint Committee on Cancer [AJCC] Staging Manual, 7th edition):

    • Stage IIIA or IIIB
    • Stage II NSCLC with medical contraindication to curative surgical resection
    • Stage IV disease with solitary brain metastasis that has been treated radically (eg: with surgical resection or stereotactic radiosurgery) and thoracic disease that would be classified as stage II-III
  • Appropriate diagnostic/staging workup, including:

    • Complete history and physical examination
    • Whole body PET/computed tomography (CT) scan within 42 days prior to study entry demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s), with a maximum standardized uptake volume (SUV) > 6 for at least one lesion.
    • Magnetic resonance imaging (MRI) of the brain or CT scan of the head with contrast within 42 days prior to study entry
    • Biopsy confirmation of suspected metastatic disease identified by PET/CT is recommended
  • No prior chemotherapy or thoracic radiotherapy for lung cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500 cells/μl
  • Platelets >= 100,000 cells/μl
  • Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
  • Total bilirubin =< 2.0 times the institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x the ULN
  • Serum creatinine =< 1.5 x ULN
  • Pulmonary function tests within 42 days prior to registration demonstrating forced expiratory volume in 1 second (FEV1) >= 1.2 liter or >= 50% predicted without bronchodilator (recommended but not required)
  • Women of childbearing potential must:

    • Have a negative serum or urine pregnancy test within 72 hours prior to the start of study therapy
    • Agree to utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study therapy is completed
    • Be advised of the importance of avoiding pregnancy during trial participation and the potential risks of an unintentional pregnancy
  • All patients must sign study specific informed consent prior to study entry

Exclusion Criteria:

  • Pleural or pericardial effusion

    • A patient with pleural effusion may be enrolled the effusion is sampled by thoracentesis and cytology is negative or the effusion is seen on axial imaging but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
  • Women who

    • Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study therapy
    • Have a positive pregnancy test at baseline
    • Are pregnant or breastfeeding
  • Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite attempts to improve glucose control by fasting duration and adjustment of medications; patients with diabetes will preferably be scheduled for PET/CT imaging in the morning, and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02073968

Locations
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Nitin Ohri    718-303-3143    nohri@montefiore.org   
Principal Investigator: Nitin Ohri         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467-2490
Contact: Madhur K. Garg    718-920-4361    aecc@aecom.yu.edu   
Principal Investigator: Madhur K. Garg         
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Principal Investigator: Nitin Ohri Albert Einstein College of Medicine of Yeshiva University
  More Information

No publications provided

Responsible Party: Nitin Ohri, Principal Investigator, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT02073968     History of Changes
Other Study ID Numbers: 2013-252, NCI-2014-00216, 2013-252, P30CA013330
Study First Received: February 26, 2014
Last Updated: June 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Albert Einstein College of Medicine of Yeshiva University:
Radiotherapy
Chemotherapy
Non-small cell lung cancer
PET

Additional relevant MeSH terms:
Thoracic Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014