Post SBRT Pulmonary Metastasectomy (PSPM) Trial

NCT ID: NCT04160143

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-14
• Study Completion Date: 2023-12-31

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.

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.

Conditions

Surgical Resection; Stereotactic Body Radiotherapy; Lung Cancer; Pulmonary Metastasectomy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SBRT followed by pulmonary metastasectomy

SBRT+Surgery

Group Type: EXPERIMENTAL

Surgical resection and stereotactic body radiation therapy (SBRT)

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Agzarian, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

McMaster University/St. Joseph's Hospital Healthcare

Hamilton, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Dr. John Agzarian, MD, MPH

Role: CONTACT

agzarij@mcmaster.ca

(905) 522-1155 ext. 32701

Housne Begum, MSc, PhD

Role: CONTACT

begumh@mcmaster.ca

(905) 522-1155 ext. 35338

Facility Contacts

John Agzarian, MD, FRCSC

Role: primary

agzarij@mcmaster.ca

905-522-1155 ext. 32701

Housne Begum, MSc, PhD

Role: backup

begumh@mcmaster.ca

905-522-1155 ext. 35338

References

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Reference Type: BACKGROUND

PMID: 25981812 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 27080402 (View on PubMed)

Widder J, Klinkenberg TJ, Ubbels JF, Wiegman EM, Groen HJ, Langendijk JA. Pulmonary oligometastases: metastasectomy or stereotactic ablative radiotherapy? Radiother Oncol. 2013 Jun;107(3):409-13. doi: 10.1016/j.radonc.2013.05.024. Epub 2013 Jun 14.

Reference Type: BACKGROUND

PMID: 23773410 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 26899780 (View on PubMed)

Junker K, Langner K, Klinke F, Bosse U, Thomas M. Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. Chest. 2001 Nov;120(5):1584-91. doi: 10.1378/chest.120.5.1584.

Reference Type: BACKGROUND

PMID: 11713138 (View on PubMed)

Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. doi: 10.1016/0360-3016(95)00060-C. No abstract available.

Reference Type: BACKGROUND

PMID: 7713792 (View on PubMed)

Begum H, Swaminath A, Lee Y, Fahim C, Bramson J, Naqvi A, Shargall Y, Finley C, Hanna W, Agzarian J. The histologic effects of neoadjuvant stereotactic body radiation therapy (SBRT) followed by pulmonary metastasectomy-rationale and protocol design for the Post SBRT Pulmonary Metastasectomy (PSPM) trial. Transl Cancer Res. 2022 Apr;11(4):918-927. doi: 10.21037/tcr-22-232.

Reference Type: DERIVED

PMID: 35571641 (View on PubMed)

Other Identifiers

SJHH_PSPM

Identifier Type: -

Identifier Source: org_study_id