Clinical Trials /

Leucoselect Phytosome for Neoadjuvant Treatment of Early Stage Lung Cancer

NCT04515004

Description:

Lung cancer is the leading cause of cancer death in the country, surpassing deaths caused by colorectal, prostate and breast cancers combined. Veterans are at higher risk of lung cancer due to the higher rate of smoking and environmental toxin exposures. The lack of effective therapy for lung cancer provides the impetus to search for alternative, safe, and effective treatment agents to improve treatment strategy against lung cancer, enhance the probability of a cure and reduce recurrence. Based on encouraging preclinical and clinical findings from an early phase I lung cancer prevention study, using a special formulation of a standardized grape seed extract with enhanced absorption called leucoselect phytosome (LP), the purpose of this new CSR&D Merit Review project is to evaluate the potential usefulness of LP for pre-surgical treatment of early stage lung cancer patients in a phase IIa clinical trial. Findings from this study may set the stage for larger, confirmatory trials in the near future.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Leucoselect Phytosome for Neoadjuvant Treatment of Early Stage Lung Cancer
  • Official Title: Leucoselect Phytosome for Neoadjuvant Treatment of Early Stage Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: ONCB-006-19F
  • SECONDARY ID: I01 CX002028
  • NCT ID: NCT04515004

Conditions

  • Early Stage Lung Cancer (I and II)

Interventions

DrugSynonymsArms
leucoselect phytosomeIntervention

Purpose

Lung cancer is the leading cause of cancer death in the country, surpassing deaths caused by colorectal, prostate and breast cancers combined. Veterans are at higher risk of lung cancer due to the higher rate of smoking and environmental toxin exposures. The lack of effective therapy for lung cancer provides the impetus to search for alternative, safe, and effective treatment agents to improve treatment strategy against lung cancer, enhance the probability of a cure and reduce recurrence. Based on encouraging preclinical and clinical findings from an early phase I lung cancer prevention study, using a special formulation of a standardized grape seed extract with enhanced absorption called leucoselect phytosome (LP), the purpose of this new CSR&D Merit Review project is to evaluate the potential usefulness of LP for pre-surgical treatment of early stage lung cancer patients in a phase IIa clinical trial. Findings from this study may set the stage for larger, confirmatory trials in the near future.

Detailed Description

      The investigators will conduct a phase IIa, single arm study using 2-3 weeks of oral LP
      treatment for 30 early stage I and II lung cancer patients before surgical resection of their
      tumors.

      Screening: Patients who have suspected early stage lung cancer will be recruited from
      Pulmonary and Thoracic Surgery clinics prior to diagnostic biopsy.

      Following informed consent, which includes allowing the investigators to collect and store
      some of the samples from the clinical diagnostic procedures as pretreatment samples, such as
      bronchoscopy, needle aspirations, etc., subject will be screened with history and physical
      examination (H & P), respiratory/general health questionnaires, food frequency
      self-assessment questionnaires, review of medical records, including radiographic imaging
      data, pulmonary function test (PFT), 12-lead EKG, clinical labs (complete blood chemistry
      panel, blood cell counts, PT, PTT). Most of these diagnostic tests will have already been
      obtained as a part of the clinical work up. However, new blood tests will be obtained if the
      last results were over 3 months ago). Blood samples and urine samples will be collected for
      research. Serum cotinine will be obtained to ascertain smoking status. A portion of the
      biospecimens (blood, urine, diagnostic samples) collected will be kept for future research at
      the NMVAHCS in an approved repository. A pregnancy test will be done for a woman who is able
      to have children.

      Intervention: (treatment with study medication). If stage I or II lung cancer is diagnosed
      from standard clinical practice, the qualified subject will be enrolled into the intervention
      study to receive 2-3 weeks of LP, taken by mouth once a day, until the lung cancer surgery.
      At the time of surgery, serial clinical samples, including bronchoscopic and various
      surgically resected tissues, blood and urine will be collected as post-treatment samples.
      Pre- and post-treatment samples will be compared to assess how well oral LP has been
      absorbed, and whether or not there are encouraging anti-cancer changes occurring in the cells
      and molecules in response to the LP treatment. Once enrolled for intervention, all subjects
      will be monitored with weekly phone follow up, the safety of LP will be monitored weekly
      using standard reporting tools (including the NCI common terminology criteria for adverse
      events Version 5.0 and adverse reaction questionnaires), as well as pre-surgery H&P and blood
      tests.

      Follow up: Post-surgery phone follow up will occur at 3-4 weeks, 6 months and annually for up
      to 4 years.
    

Trial Arms

NameTypeDescriptionInterventions
InterventionExperimentalAll qualified participants meeting entry criteria that are enrolled will receive 2-3 weeks of oral LP treatment.
  • leucoselect phytosome

Eligibility Criteria

        Inclusion Criteria:

        A. Initial screening:

          -  Lesions suspicious for lung cancer

          -  Competent to provide consent

          -  CBC within normal limits (WNL)

          -  liver function test WNL

          -  Normal Creatinine clearance as measured by the Cockcroft-Gault equation

          -  ECOG Performance status: 0-1

        B. Enrollment for treatment with LP:

          -  Histologically proven and surgically resectable clinical I and II stage NSCLC

        Exclusion Criteria:

          -  Inability to provide informed consent (e.g. cognitive impairment, severe psychiatric
             disorders)

          -  Hypersensitivity to grapes or related products

          -  Advance respiratory disease (Post resection FEV1 < 0.8 liters, resting hypoxemia, to
             ensure pts have adequate reserve to undergo diagnostic procedures and surgical
             resection)

          -  Unstable angina

          -  Other concurrent malignancy, excluding non-melanoma type skin cancer

          -  Have had a solid organ or bone marrow transplant

          -  Pregnancy

          -  Breast feeding

          -  Systemic corticoid steroid therapy of > 10 mg prednisone equivalent daily

          -  Coagulopathy (PT-INR > 1.2, PTT > 40 seconds) or history of bleeding/clotting problems

          -  Concurrent use of Grapes or related products

          -  Unwilling to refrain from drinking more than 1 glass of wine a day

          -  Pts receiving medications known to be modulators of cytochrome P450 3A4 if alternative
             medication cannot be provided

          -  Currently taking other investigational agents

          -  Pts with concurrent medical conditions that may interfere with completion of tests,
             therapy, or the follow up schedule
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Delay in the planned surgery of >14 days that is possibly related to study medication (Safety and feasibility).
Time Frame:No greater than 14 days delay in planned surgery.
Safety Issue:
Description:Defined as no delay in the planned surgery of >14 days that is possibly related to study medication.

Secondary Outcome Measures

Measure:Tumor Ki-67 labeling index (LI), a marker of cell proliferation.
Time Frame:Interim analysis on matched, pre- and post-treatment comparisons will be performed after 10 subjects have completed the treatment portion of the study, anticipated to be in year 2
Safety Issue:
Description:Modulations of tumor Ki-67 LI.
Measure:Histopathology: pathological response of resected tumor and Lymph nodes.
Time Frame:Interim analysis on matched, pre- and post-treatment comparisons will be performed after 10 subjects have completed the treatment portion of the study, anticipated to be in year 2
Safety Issue:
Description:Tumors and lymph nodes with no more than 10% viable tumor cells will be considered to have had a major pathological response.
Measure:Tumor activated caspase 3.
Time Frame:Interim analysis on matched, pre- and post-treatment comparisons will be performed after 10 subjects have completed the treatment portion of the study, anticipated to be in year 2
Safety Issue:
Description:Modulations of this marker of apoptosis in tumors.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:VA Office of Research and Development

Trial Keywords

  • Grape seed procyanidin extract
  • Early stage lung cancer
  • Neoadjuvant treatment

Last Updated

August 18, 2020