Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma

Sponsor

Children's Oncology Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT05235165

Collaborator

National Cancer Institute (NCI) (NIH)

250

Enrollment

Locations

Arms

69.9

Anticipated Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Malignant Neoplasm in the Lung Metastatic Osteosarcoma Osteosarcoma	Other: Questionnaire Administration Procedure: Thoracoscopy Procedure: Thoracotomy	Phase 3

Detailed Description

PRIMARY OBJECTIVE:

To determine if open surgical resection is superior to thoracoscopic resection for thoracic event-free survival (tEFS) in patients with resectable oligometastatic pulmonary osteosarcoma.

SECONDARY OBJECTIVES:

To determine if open surgical resection is superior to thoracoscopy for event free survival (EFS) in patients with resectable oligometastatic pulmonary osteosarcoma.
To determine if open surgical resection is superior to thoracoscopy for overall survival (OS) in patients with resectable oligometastatic pulmonary osteosarcoma.
To determine if thoracoscopy is superior to open surgical resection for post-operative pain interference in patients with resectable oligometastatic pulmonary osteosarcoma.

EXPLORATORY OBJECTIVES:

To compare 30-day rates of perioperative surgical complications for both open surgical resection and thoracoscopy.
To compare patterns of recurrence (ipsilateral and/or contralateral) in patients who undergo open or thoracoscopic resection for unilateral or bilateral pulmonary metastases.
To describe the use of localization techniques and its relationship with both surgical approach and pathologic findings.
To assess the prognostic significance of a decision to change the post-operative treatment plan.
To describe the relationship between the preoperative chest computed tomography (CT) imaging, intraoperative surgical findings, and pathologic results, comparing radiological features to the presence of viable tumor.
To prospectively compare between treatment arms the relationship between surgical approach and patient-reported outcomes (PROs), specifically patient functional impairment of the upper extremities, pain intensity, and health-related quality of life (HRQoL).
To generate well-characterized, clinically-annotated, distributable models of metastatic osteosarcoma.
To collect and bank pulmonary metastatic lesions (including frozen tissues and paired metastatic lesions coming from the same patient) to facilitate study of metastatic disease and serial blood samples for future tumor profiling, germline and circulating tumor deoxyribonucleic acid (DNA) studies.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM A: Patients undergo open thoracic surgery (thoracotomy).

ARM B: Patients undergo thoracoscopy (video-assisted thoracoscopic surgery or VATS).

After completion of study treatment, patients are followed up at 7-14 days, 4-6 weeks, and 3 months post-surgery and then every 3 months for up to 2 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Randomized Controlled Trial Comparing Open vs Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma

Actual Study Start Date :

Feb 15, 2022

Anticipated Primary Completion Date :

Dec 15, 2027

Anticipated Study Completion Date :

Dec 15, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (thoracotomy) Patients undergo open thoracic surgery (thoracotomy).	Other: Questionnaire Administration Ancillary studies Procedure: Thoracotomy Undergo open thoracic surgery
Experimental: Arm B (thoracoscopy) Patients undergo thoracoscopy (video-assisted thoracoscopic surgery or VATS).	Other: Questionnaire Administration Ancillary studies Procedure: Thoracoscopy Undergo video-assisted thoracoscopic surgery or VATS

Arm

Intervention/Treatment

Experimental: Arm A (thoracotomy)

Patients undergo open thoracic surgery (thoracotomy).

Other: Questionnaire Administration

Ancillary studies

Procedure: Thoracotomy

Undergo open thoracic surgery

Experimental: Arm B (thoracoscopy)

Patients undergo thoracoscopy (video-assisted thoracoscopic surgery or VATS).

Other: Questionnaire Administration

Ancillary studies

Procedure: Thoracoscopy

Undergo video-assisted thoracoscopic surgery or VATS

Outcome Measures

Primary Outcome Measures

Thoracic event-free survival (tEFS) [Four years after enrollment]
Estimated four year thoracic event free survival (tEFS) where tEFS is calculated as the time from study enrollment. Any recurrence within the pulmonary parenchyma, involving the pleural surface or the drain/surgical site wound will be considered an event. A death that results from the procedure, as confirmed by the treating physician, will be considered an event. Patients with recurrences arising outside the thoracic region, the diagnosis of a malignancy that is not osteosarcoma (SMN) or death considered unrelated to the study surgical procedure, as confirmed by the treating physician will be considered competing events provided these occur prior to a thoracic cavity event as defined above. Patients without an event of any kind at last contact are considered censored.

Secondary Outcome Measures

Event free survival (EFS) [Four years after enrollment]
Estimated four year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Patients without an event at last contact are considered censored.
Overall survival (OS) [Four years after enrollment]
Time from study enrollment to death or last patient contact. Patients alive at last contact are considered censored.
Post operative pain interference at time point 3, 7-14 days after surgical intervention [7-14 days after surgical intervention]
Total PROMIS pain interference score from the 8 item PROMIS pain interference short form.
Post operative pain interference at time point 4, 4-6 weeks after surgical intervention [4-6 weeks after surgical intervention]
Total PROMIS pain interference score from the 8 item PROMIS pain interference short form.

Other Outcome Measures

Perioperative surgical complications [At 30 days post-op]
The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be utilized for AE reporting.
Mode of tEFS event [Four years after enrollment]
Classified as: (1) ipsilateral recurrence site; (2) contralateral recurrence site; or (3) ipsilateral and contralateral recurrence site. The analysis will be restricted to patients with unilateral disease at enrollment.
Use of localization techniques [12 months after enrollment]
Data collection will include a description of all localization methods used.
Decision to change the post-operative treatment plan [12 months after enrollment]
Whether the investigator adhered to the post-thoracic surgery plan for systemic therapy.
Radiological features to the presence of viable tumor [12 months after enrollment]
Radiological features and pathological characteristics of lung nodules contributed by the same patient.
Post operative upper extremity function at time point 2, 24-48 hours after surgical intervention [24-48 hours after surgical intervention]
Total PROMIS upper extremity score from the 8 item PROMIS upper extremity short form.
Post operative upper extremity function at time point 3, 7-14 days after surgical intervention [7-14 days after surgical intervention]
Total PROMIS upper extremity score from the 8 item PROMIS upper extremity short form.
Post operative pain intensity at time point 2, 24-48 hours after surgical intervention [24-48 hours after surgical intervention]
NRS 11 single item pain intensity score.
Post operative pain intensity at time point 3, 7-14 days after surgical intervention [7-14 days after surgical intervention]
NRS 11 single item pain intensity score.
Frequency of obtaining quality tumor tissue for biological analysis [1 month after surgical intervention]
Tumor samples obtained from the surgical procedure that are submitted to the COG tissue bank and subjected to dual nucleic acid extraction will be classified by central review as to whether sufficient tumor content was obtained for ultra low passage whole genome sequencing.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must be < 50 years at the time of enrollment.
Patient must have eligibility confirmed by rapid central imaging review.
Patients must have =< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
Patients must have a histological diagnosis of osteosarcoma.
Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
Newly diagnosed patients must be receiving systemic therapy considered by the treating physician as at least equivalent to methotrexate, doxorubicin and cisplatin (MAP) at the time of enrollment on this study.
Patients at time of 1st recurrence must have previously completed initial systemic therapy for their primary tumor, considered by the treating physician as at least equivalent to MAP.

Exclusion Criteria:

Patients with unresectable primary tumor.
Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
Patients with pleural or mediastinal based metastatic lesions, or with pleural effusion.
Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
Patients with evidence of extrapulmonary metastatic disease.
Patients who received pulmonary surgery for lung metastasis prior to enrollment.
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Banner Children's at Desert	Mesa	Arizona	United States	85202
3	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
5	Kaiser Permanente-Oakland	Oakland	California	United States	94611
6	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
7	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
8	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
9	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
10	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
11	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
12	Nemours Children's Hospital	Orlando	Florida	United States	32827
13	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
14	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
15	University of Illinois	Chicago	Illinois	United States	60612
16	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
17	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
18	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
19	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
20	Eastern Maine Medical Center	Bangor	Maine	United States	04401
21	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
22	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
23	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
24	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
25	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
26	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
27	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
28	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
29	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
30	Ascension Borgess Cancer Center	Kalamazoo	Michigan	United States	49009
31	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
32	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
33	Lakeland Hospital Niles	Niles	Michigan	United States	49120
34	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan	United States	49444
35	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
36	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
37	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
38	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
39	Munson Medical Center	Traverse City	Michigan	United States	49684
40	Metro Health Hospital	Wyoming	Michigan	United States	49519
41	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
42	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
43	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
44	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
45	Mount Sinai Hospital	New York	New York	United States	10029
46	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
47	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
48	New York Medical College	Valhalla	New York	United States	10595
49	Westchester Medical Center	Valhalla	New York	United States	10595
50	Duke University Medical Center	Durham	North Carolina	United States	27710
51	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
52	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
53	Dayton Children's Hospital	Dayton	Ohio	United States	45404
54	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
55	Oregon Health and Science University	Portland	Oregon	United States	97239
56	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
57	Rhode Island Hospital	Providence	Rhode Island	United States	02903
58	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
59	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
60	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
61	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
62	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
63	El Paso Children's Hospital	El Paso	Texas	United States	79905
64	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
65	M D Anderson Cancer Center	Houston	Texas	United States	77030
66	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
67	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
68	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
69	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
70	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
71	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
72	Madigan Army Medical Center	Tacoma	Washington	United States	98431
73	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
74	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
75	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5

Sponsors and Collaborators

Children's Oncology Group
National Cancer Institute (NCI)

Investigators

Principal Investigator: John J Doski, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Children's Oncology Group

ClinicalTrials.gov Identifier:

NCT05235165

Other Study ID Numbers:

AOST2031
NCI-2021-14237
AOST2031
AOST2031
U10CA180886

First Posted:

Feb 11, 2022

Last Update Posted:

Aug 18, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Additional relevant MeSH terms:

Neoplasms

Osteosarcoma

Study Results

No Results Posted as of Aug 18, 2022