Post SBRT Pulmonary Metastasectomy (PSPM) Trial (PSPM)

February 23, 2021 updated by: McMaster University

Evaluating the Histologic Effects of Neoadjuvant Stereotactic Body Radiation Therapy (SBRT) Followed by Pulmonary Metastasectomy-Post SBRT Pulmonary Metastasectomy (PSPM) Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Dr. John Agzarian, MD, MPH
  • Phone Number: 32701 (905) 522-1155
  • Email: agzarij@mcmaster.ca

Study Contact Backup

  • Name: Housne Begum, MSc, PhD
  • Phone Number: 35338 (905) 522-1155
  • Email: begumh@mcmaster.ca

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • Recruiting
        • McMaster University/St. Joseph's Hospital Healthcare
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
post-operative 3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Post operative 3 years
Followup over all survival (OS) at 3 years
Post operative 3 years
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
Disease-free survival (DFS) at 3 years
local recurrence rates
Time Frame: post operative 3 years
CT scan at follow-up
post operative 3 years
Radiation related toxicity
Time Frame: Post radiation 1 year
Follow Radiation Therapy Oncology Group (RTOG) Common Toxicity Criteria (Cox, 1995)
Post radiation 1 year
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
post operative 30 days
The effect on time-to-resection and tumour histology on pCR
Time Frame: 8 to 12 weeks at different time post operative
Time analysis
8 to 12 weeks at different time post operative
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.
Baseline/ pre-SBRT; 6 Weeks post SBRT/6 weeks post Radiation , 6 weeks post Surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Investigators

  • Principal Investigator: John Agzarian, MD, MPH, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2020

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

October 29, 2019

First Submitted That Met QC Criteria

November 7, 2019

First Posted (Actual)

November 12, 2019

Study Record Updates

Last Update Posted (Actual)

February 25, 2021

Last Update Submitted That Met QC Criteria

February 23, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SJHH_PSPM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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