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Post SBRT Pulmonary Metastasectomy (PSPM) Trial (PSPM)

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ClinicalTrials.gov Identifier: NCT04160143
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : February 25, 2021
Sponsor:
Information provided by (Responsible Party):
McMaster University

Brief Summary:
The goal of this study is to determine the effectiveness of SBRT on reducing tumor viability at a pathologic level and also to evaluate the effects of combined modality treatment on low volume pulmonary metastases, in hopes of extrapolating this information to both primary and secondary lung cancer.

Condition or disease Intervention/treatment Phase
Surgical Resection Stereotactic Body Radiotherapy Lung Cancer Pulmonary Metastasectomy Procedure: Surgical resection and stereotactic body radiation therapy (SBRT) Not Applicable

Detailed Description:

The role of SBRT as a potentially non-invasive treatment for small-volume tumors in the lung is well established, but the effectiveness of tumor eradication has yet to be determined. This prospective Phase 2 trial will provide several novel contributions to the literature: 1) the assessment of SBRT effectiveness in metastatic tumor control (radiotherapeutic metastasectomy), 2) the evaluation of pathologic response to SBRT by surgical resection, 3) identification of histologic predictors of radiation effect and toxicity (i.e. what are the effects of SBRT on different type of metastatic disease), and 4) the effect of combined modality SBRT and surgery on survival and local recurrence as compared to either modality alone. This trial will uniquely assess whether surgery as an adjunct to radiotherapy offers better tumor control as compared to SBRT alone, and whether it decreases locoregional recurrence. The study is an open-label unblinded single-arm prospective trial evaluating induction SBRT followed by pulmonary metastasectomy. This is a collaborative effort between the divisions of Thoracic Surgery and Radiation Oncology to evaluate the effects of dual treatment of pulmonary metastasis amenable to curative resection with neoadjuvant SBRT followed by surgical resection. Study recruitment and analysis will be conducted at St. Joseph Healthcare Hamilton and the Juravinski Cancer Center. Institutional data suggests that the Division of Thoracic Surgery at McMaster University performs an average of 450 pulmonary resections per year with approximately 10-15% being pulmonary metastasectomies for a spectrum of malignancies (including colorectal carcinoma, renal cell carcinoma and soft tissue sarcoma).

Surgical resection and stereotactic body radiation therapy (SBRT) are generally regarded as mutually exclusive treatment options for the local management of pulmonary malignancies. The Primary Outcome will be measured as the Rates of complete pathologic response (pCR) in surgical specimens post SBRT as assessed using the Junker grading scale for lung malignancies: Grade I, no regression or only spontaneous tumor regression; Grade II, morphologic evidence of tumor regression with at least 10% (grade IIa) or <10% (grade IIb) viable tumor tissue; and Grade III, complete tumor regression with no viable tumor. The Secondary Outcomes: Overall survival (OS) at 3 years, Disease-free survival (DFS) at 3 years, local recurrence rates, radiation related toxicity, postoperative pulmonary complication rate (including prolonged air leak, need for invasive or noninvasive mechanical ventilation, postop pneumonia and empyema), the effect on time-to-resection and tumour histology on pCR. In addition, it will be explored whether cancer specific tumor biomarkers correlate with SBRT effects and related toxicity. Based on institutional data from other local prospective trials, the Thoracic Surgery division at McMaster averages a study accrual rate of 25-30% and retention rate of approximately 80%. The most pertinent metric in determining the necessary sample size is the effect size estimate of pCR. The MISSILE study preliminary data demonstrated a pCR of 60%. This serves as the only representative value in the literature, even though our study evaluates SBRT and surgery for metastatic disease and NOT primary lung cancer. In contrast, the SBRT literature (using post-treatment CT scan surveillance only) reports local control rates of nearly 90%. Using the Fleming procedure, in order to measure the true pCR with a 95% confidence interval ± 10% using an estimated true pCR of 70%, estimated dropout rate of 20%, and 80% power, the calculated sample size requirement is 39 patients. It is estimated being able to recruit approximately 1-2 patients per month.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This innovative study is an open-label unblinded single-arm prospective trial evaluating induction SBRT followed by pulmonary metastasectomy. As a Phase 2 trial, the primary purpose is to assess the efficacy of SBRT on metastatic tumor viability and the safety of SBRT as induction treatment prior to surgery
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluating the Histologic Effects of Neoadjuvant Stereotactic Body Radiation Therapy (SBRT) Followed by Pulmonary Metastasectomy-Post SBRT Pulmonary Metastasectomy (PSPM) Trial
Actual Study Start Date : July 14, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SBRT followed by pulmonary metastasectomy
SBRT+Surgery
Procedure: Surgical resection and stereotactic body radiation therapy (SBRT)
Surgical resection and stereotactic body radiation therapy (SBRT) are generally regarded as mutually exclusive treatment options for the local management of pulmonary malignancies. This Phase 2 prospective trial is a collaborative effort between the divisions of Thoracic Surgery and Radiation Oncology to evaluate the effects of dual treatment of pulmonary metastasis amenable to curative resection with neoadjuvant SBRT followed by surgical resection.




Primary Outcome Measures :
  1. Rates of complete pathologic response (pCR) [ Time Frame: post-operative 3 weeks ]
    pCR in surgical specimens post SBRT as assessed using the Junker grading scale for lung malignancies: Grade I, no regression or only spontaneous tumor regression; Grade II, morphologic evidence of tumor regression with at least 10% (grade IIa) or <10% (grade IIb) viable tumor tissue; and Grade III, complete tumor regression with no viable tumor.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Post operative 3 years ]
    Followup over all survival (OS) at 3 years

  2. Disease-free survival (DFS) [ Time Frame: Disease-free survival (DFS) at 3 years ]
    Followup over all survival (OS) at 3 years. Based on 1. clinical 2. CT scan results

  3. local recurrence rates [ Time Frame: post operative 3 years ]
    CT scan at follow-up

  4. Radiation related toxicity [ Time Frame: Post radiation 1 year ]
    Follow Radiation Therapy Oncology Group (RTOG) Common Toxicity Criteria (Cox, 1995)

  5. Postoperative pulmonary complication rate (including prolonged air leak, need for invasive or noninvasive mechanical ventilation, postop pneumonia and empyema) [ Time Frame: post operative 30 days ]
    Using Society of Thoracic Surgery (STS) Database

  6. The effect on time-to-resection and tumour histology on pCR [ Time Frame: 8 to 12 weeks at different time post operative ]
    Time analysis

  7. Identify mRNA tumor markers by Circulating Tumor Cell/CTC test [ Time Frame: Baseline/ pre-SBRT; 6 Weeks post SBRT/6 weeks post Radiation , 6 weeks post Surgery ]
    Identify mRNA tumor markers for circulating tumor cell/CTC detection from blood sample to get cancer specific tumor biomarkers correlate with SBRT effects including different targeted gene such MUC1, HER2, EPCAM, ER/PR for Breast Cancer, PSA, PSMA, EGFR, AR for Prostate Cancer, EPCAM, EGFR, CEA for Colon Cancer, EPCAM, MUC1, CA125, ERCC1 for Ovarian Cancer and Stemcell . The CTC test will be doing to get information about whether or not disease has disseminated from the primary site and mainly as a prognostic and/or predictive marker in the metastatic settings. This test will be done in baseline or Pre SBRT, Post SBRT and Post Surgery.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age >18, resectable pulmonary metastases without a more effective systemic therapy option (regardless of type of primary malignancy, excluding hematologic malignancies) with the primary malignancy already having been treated without evidence of local recurrence
  • Patient having single-organ metastasis to lung only (with the exception of colorectal CA (Cancer) with synchronous hepatic metastasis)
  • Tumors <5cm
  • Patient with no evidence of nodal disease on pre-treatment CT scan
  • Patient having adequate pulmonary function to tolerate lung resection (post-operative predictive FEV1≥40%).

Exclusion Criteria:• Patient having comorbidities not amenable to surgery

  • Patient with uncontrolled primary malignancy
  • Patient with hematologic malignancies (leukemia or lymphoma)
  • Patient having more than 5 tumors in one lung
  • Patient with prior history of thoracic radiation
  • Patient having history of lung cancer diagnosis within 5 years of assessment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04160143


Contacts
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Contact: Dr. John Agzarian, MD, MPH (905) 522-1155 ext 32701 agzarij@mcmaster.ca
Contact: Housne Begum, MSc, PhD (905) 522-1155 ext 35338 begumh@mcmaster.ca

Locations
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Canada, Ontario
McMaster University/St. Joseph's Hospital Healthcare Recruiting
Hamilton, Ontario, Canada, L8N 4A6
Contact: John Agzarian, MD, FRCSC    905-522-1155 ext 32701    agzarij@mcmaster.ca   
Contact: Housne Begum, MSc, PhD    905-522-1155 ext 35338    begumh@mcmaster.ca   
Sponsors and Collaborators
McMaster University
Investigators
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Principal Investigator: John Agzarian, MD, MPH McMaster University
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT04160143    
Other Study ID Numbers: SJHH_PSPM
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by McMaster University:
Surgical resection
Stereotactic body radiation therapy
Pulmonary metastasectomy
Lung Cancers
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases