Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446911
Recruitment Status : Unknown
Verified February 2018 by A.J. de Langen, VU University Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : February 27, 2018
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
A.J. de Langen, VU University Medical Center

Tracking Information
First Submitted Date  ICMJE November 8, 2017
First Posted Date  ICMJE February 27, 2018
Last Update Posted Date February 27, 2018
Estimated Study Start Date  ICMJE March 2018
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
Incidence and severity of adverse events in patients treated by combining SBRT and pembrolizumab [ Time Frame: Up to 90 days post-treatment ]
Safety of the combination of SBRT and pembrolizumab will be assessed by the percentage of ≥3 pneumonitis. When combined SBRT and pembrolizumab treatment results in NCIC-CTC grade ≥3 pneumonitis in ≤10% of patients, the combination is regarded as safe. Serious adverse events will be recorded to assess both incidence and severity.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
  • PD-1 expression [ Time Frame: Up to 90 days post-treatment ]
    PD-1 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.
  • PD-L1 expression [ Time Frame: Up to 90 days post-treatment ]
    PD-L1 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.
  • CD4 expression [ Time Frame: Up to 90 days post-treatment ]
    CD4 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.
  • CD8 expression [ Time Frame: Up to 90 days post-treatment ]
    CD8 expression in tumor tissue, TDLN's and peripheral blood.
  • FoxP3 expression [ Time Frame: Up to 90 days post-treatment ]
    FoxP3 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.
  • Ki67 expression [ Time Frame: Up to 90 days post-treatment ]
    Ki67 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.
  • Immune cell count [ Time Frame: Up to 90 days post-treatment ]
    Cell count of the individual immune cells in tumordraining lymphnodes and non-tumordraining lymphnodes
  • Analysis of PET data - SUVmax (standardized uptake value) [ Time Frame: Up to 90 days post-treatment ]
    SUVmax will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.
  • Analysis of PET data - SUVpeak (standardized uptake value) [ Time Frame: Up to 90 days post-treatment ]
    SUVpeak will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.
  • Analysis of PET data -SUVmean (standardized uptake value) [ Time Frame: Up to 90 days post-treatment ]
    SUVmean will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.
  • Analysis of CT data - Hounsfield Unit density [ Time Frame: Up to 90 days post-treatment ]
    The pre- and post SBRT +/- pembrolizumab CT scans will be assessed for HU density and f-air values
  • Analysis of CT data - f-air values [ Time Frame: Up to 90 days post-treatment ]
    The pre- and post SBRT +/- pembrolizumab CT scans will be assessed for and f-air values
  • Correlation between PET data and Blood + Tissue markers [ Time Frame: Up to 90 days post-treatment ]
    The data of the PET-scan will be analyzed and compared to the blood and tissue samples to find a correlation between findings.
  • Correlation between tumor uptake of Zr89-pembrolizumab and irAEs [ Time Frame: Up to 90 days post-treatment ]
    SUV are values used to describe PET-data. irAE's are specific adverse events. This outcome aims to correlate the (possible) irAE's with the PET-data.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery
Official Title  ICMJE Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery: Exploring Safety and Immunological Proof of Principle.
Brief Summary This study aims to evaluate the safety and mechanisms of action of the trimodality treatment (radiotherapy, immunotherapy and surgery) in early-stage non-small cell lung cancer. Half of the patients will receive stereotactic ablative radiotherapy followed by 2 cycles of immunotherapy (pembrolizumab); the other half will not receive the immunotherapy treatment. After treatment, both groups will continue treatment according to guidelines and will undergo surgery (lobectomy).
Detailed Description

An open label randomized exploratory study of the safety and mechanisms of action of combined treatment with SBRT and immunotherapy (pembrolizumab, anti-PD1) for early stage NSCLC.

Intervention:

Patients will be randomized between SBRT with or without 2 cycles of pembrolizumab treatment (starting on the first day of radiotherapy). The patients will undergo a lobectomy with hilar and mediastinal lymph node dissection after SBRT +/- pembrolizumab treatment. Translational research to explore the immune mechanism of action will include biological imaging with immuno-PET (positron emission tomography). Expression rates and activation states of immune effector subsets will be assessed in tumor core biopsy specimens, peripheral blood and tumor draining lymph nodes (TDLNs) by means of fine needle aspirates of TDLNs.

Main study parameters/endpoints:

To assess the safety of combined SBRT and pembrolizumab treatment in early stage NSCLC and to identify the immunological mechanism of action.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE NSCLC, Stage I
Intervention  ICMJE
  • Radiation: SABR
    Prior to surgery (lobectomy), patients receive stereotactic ablative radiotherapy.
  • Combination Product: SABR + pembrolizumab
    Prior to surgery (lobectomy), patients receive stereotactic ablative radiotherapy + 2 rounds of pembrolizumab
Study Arms  ICMJE
  • Active Comparator: SABR
    Patients receive prior to surgery (lobectomy) SABR.
    Intervention: Radiation: SABR
  • Active Comparator: SABR + pembrolizumab
    Patients receive prior to surgery (lobectomy) SABR + 2 rounds of pembrolizumab
    Intervention: Combination Product: SABR + pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 20, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Have a histologically or cytologically confirmed diagnosis of early stage (T1bN0 and T2aN0) peripherally located NCSLC, eligible for surgical resection.
  2. Be willing and able to provide written informed consent/assent for the trial.
  3. Be 18 years of age or over on day of signing informed consent.
  4. Have measurable disease based on RECIST 1.1.
  5. Must provide tissue from a core or excisional biopsy of the primary tumor lesion.
  6. Have a performance status of 0-1 on the ECOG Performance Scale.
  7. Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
  8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  • 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.

    2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

    3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

    4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

    6. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.

    7. Has a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.

    8. Has an active infection requiring systemic therapy. 9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

    10. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

    11. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

    12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

    13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

    14. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

    15. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03446911
Other Study ID Numbers  ICMJE MK3475-586
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party A.J. de Langen, VU University Medical Center
Study Sponsor  ICMJE VU University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: E.F. Smit, MD, PhD The Netherlands Cancer Institute
Study Chair: A.J. de Langen, MD, PhD The Netherlands Cancer Institute
PRS Account VU University Medical Center
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP