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A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer

NCT02492867

Description:

Successful treatment of lung cancer with radiation therapy requires that the physicians determine exactly where the tumor is in the patient's body and seek to limit any unnecessary radiation to normal parts of the body. This study is designed to apply functional imaging, Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) ("a PET scan") and Ventilation/Perfusion Single Photon Emission Computerized Tomography (V/Q SPECT) ("a perfusion scan"), before treatment and then again during treatment to see if this scanning helps predict how well the treatment works and how well the lung functions during treatment. FDG-PET is a modern technology that uses small amounts of a radioactive glucose (FDG) to make images of the whole body and areas of active cancer. V/Q SPECT is an image mapping tool that helps assess how well the lungs are working. A Computerized Tomography (CT) will also be performed along with both of these procedures to help the researchers see clearly where the cancer or the healthy lung is located. The researchers are also doing blood and urine tests in this study to look for markers to see if this helps them determine the patient's risk of developing side effects from radiation to the lungs. The researchers hope by using these types of tests that they can have more information to help decrease the amount of toxicity patients have from this type of treatment. The researchers hope that this study will help them in the future to design radiation treatment plans that provide the best treatment for each individual patient.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer
  • Official Title: A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2015.035
  • SECONDARY ID: HUM00098202
  • NCT ID: NCT02492867

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
CarboplatinResponse-driven Adaptive RT
PaclitaxelResponse-driven Adaptive RT
DurvalumabResponse-driven Adaptive RT

Purpose

Successful treatment of lung cancer with radiation therapy requires that the physicians determine exactly where the tumor is in the patient's body and seek to limit any unnecessary radiation to normal parts of the body. This study is designed to apply functional imaging, Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) ("a PET scan") and Ventilation/Perfusion Single Photon Emission Computerized Tomography (V/Q SPECT) ("a perfusion scan"), before treatment and then again during treatment to see if this scanning helps predict how well the treatment works and how well the lung functions during treatment. FDG-PET is a modern technology that uses small amounts of a radioactive glucose (FDG) to make images of the whole body and areas of active cancer. V/Q SPECT is an image mapping tool that helps assess how well the lungs are working. A Computerized Tomography (CT) will also be performed along with both of these procedures to help the researchers see clearly where the cancer or the healthy lung is located. The researchers are also doing blood and urine tests in this study to look for markers to see if this helps them determine the patient's risk of developing side effects from radiation to the lungs. The researchers hope by using these types of tests that they can have more information to help decrease the amount of toxicity patients have from this type of treatment. The researchers hope that this study will help them in the future to design radiation treatment plans that provide the best treatment for each individual patient.

Detailed Description

      This is a pilot study to improve local tumor control while maintaining the same rate of
      treatment toxicity by adapting therapy to the uninvolved lung and esophagus while continuing
      to adapt therapy to the tumor for patients with Stage II/III NSCLC.

      Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2012,
      there were 226,160 new cases and 160,340 deaths related to lung cancer in the United States.
      Approximately, 80-85% of lung cancers are NSCLC (Non-small Cell Lung Cancer), and 40% of
      these are locally advanced (stage II/III) at diagnosis. The current standard of care for
      these patients is "one size fits all" RT (Radiation Therapy) with concurrent chemotherapy in
      uniform regimens. Even after concurrent chemoradiation, however, the five year overall
      survival was still about 15%; almost one half of the patients failed locally. At the same
      time, intensification of both radiotherapy and concurrent chemotherapy may result in
      excessive toxicity or incomplete treatment. Therefore, it is critical to tailor the treatment
      to each individual's sensitivity in combination with functional imaging guided
      response-driven treatment and biomarker guided individualized dose prescription, thus taking
      into consideration both the tumor and toxicity profile.

      Evidence suggests that high-dose radiation has the potential to improve local-regional
      control and overall survival in patients treated with fractionated therapy with concurrent
      chemotherapy.

      However, it is challenging to deliver high dose RT in the majority of patients with locally
      advanced NSCLC without exceeding doses to organs at risk and causing significant side
      effects.

      Investigators hypothesized that they could develop safer and more effective therapy by
      adapting treatment to the individual patient's response. With respect to the tumor,
      investigators hypothesized, that they could improve outcome by redistributing dose to the
      more aggressive regions of the tumor, assessed using mid-treatment FDG-PET (Positron Emission
      Tomography) scanning. With respect to uninvolved organs, investigators need methods of
      estimating tolerable radiation doses for the individual patient rather than the population
      average. Such a strategy requires assessing both global and regional normal lung function and
      the technology to deliver dose in a manner that minimizes damage to functional lung and
      esophagus.

      During-RT FDG-PET/CT potentially can provide important benefits to individual patients by
      intensifying dose to more resistent tumor, allowing early changes to alternative, more
      efficacious treatment or by avoiding the unnecessary toxicity related to ineffective therapy.

      Patients will also undergo a during treatment V/Q SPECT (Single-photon Emission Computed
      Tomography) scan, as an adaptive plan based on during-treatment SPECT may further optimize
      PART (Personalized Adaptive Radiotherapy) to avoid high dose radiation to the
      well-functioning regions, and would thus decrease RILT (Radiation Induced Lung Toxicity).

      The combination of pre- and during V/Q SPECT can classify the lung into different functional
      regions, and a strategy to give differential priority to the regions has been developed to
      minimize lung damage.

      Investigators plan to continue to collect data on serum biomarkers to further refine their
      biophysical model with the ultimate goal of individualizing radiation dose prescription.

      By identifying high risk patients and adjusting OAR (Organs at Risk) dose limits to the
      threshold of tolerance, investigators anticipate a significant reduction in the incidence of
      toxicity from UMCC 2007.123 (NCT01190527) without compromised tumor control by applying the
      model to optimize radiation planning.
    

Trial Arms

NameTypeDescriptionInterventions
Response-driven Adaptive RTExperimentalPatients will receive treatment 5 days per week, in once daily fractions, for 30 treatments with dose per fraction individually adapted over the final 9 treatments. Patients may also receive concurrent chemotherapy with Carboplatin and Paclitaxel. Patients may receive consolidation chemotherapy (carboplatin and paclitaxel) or immunotherapy (durvalumab) at the discretion of the medical oncologist.
  • Carboplatin
  • Paclitaxel
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have FDG-avid and pathologically proven Stage IIA-IIIB non-small cell
             lung cancer.

          -  Patients must be considered unresectable or inoperable.

          -  Patients must be 18 years of age or older.

          -  Patients must have a Karnofsky performance (A measure general well-being and
             activities of daily life. Scores range between 0 and 100 where 100 represents normal
             and 0 represents death.) of score > or = to 70.

          -  Patients must have adequate organ and marrow function.

          -  Patient must be willing to use effective contraception if female with reproductive
             capability.

          -  Patients must be informed of the investigational nature of this study and given
             written informed consent in accordance with institutional and federal guidelines.

        Exclusion Criteria:

          -  Patients with any component of small cell lung carcinoma

          -  Patients with evidence of a malignant pleural or pericardial effusion

          -  Prior radiotherapy to the thorax such that composite radiation would significantly
             overdose critical structures, either per estimation of the treating radiation
             oncologist or defined by failure to meet normal tissue tolerance constraints

          -  Patients cannot tolerate concurrent chemotherapy

          -  Pregnant women are excluded from this study because radiation has the potential for
             teratogenic or abortifacient effects.

          -  Prisoners are excluded for this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of patients for whom treatment is feasible.
Time Frame:6 weeks (30 treatments, 5 days per week)
Safety Issue:
Description:To determine the feasibility of the proposed adaptive treatment strategy, we will look at the number of patients for whom treatment is feasible. Treatment is feasible if we are able to deliver the full treatment, using the image based spatial replanning and complete the cytokine assays in a short enough timeframe to adapt radiation dose.

Secondary Outcome Measures

Measure:Time to local progression
Time Frame:Up to 60 months
Safety Issue:
Description:Defined as the time from start of treatment to time of local/regional progression on PET, summarized with the Kaplan-Meier method.
Measure:Overall survival time
Time Frame:Up to 60 months
Safety Issue:
Description:Defined as the time from start of treatment to death.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

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