Clinical trial NCT06526897: Evaluation of Chest CT Versus Chest X-Ray for Lung Surveillance After Curative-Intent Resection of High-Risk Truncal-Extremity Soft Tissue Sarcoma
Official title: A Phase III Randomized Controlled Trial of Chest CT vs Chest X-Ray for Lung Surveillance After Curative-Intent Resection of High-Risk Truncal-Extremity Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Adult Pleomorphic Rhabdomyosarcoma
AJCC Grade 2 Sarcoma
AJCC Grade 3 Sarcoma
Alveolar Soft Part Sarcoma
Angiosarcoma
Clear Cell Sarcoma of Soft Tissue
Dedifferentiated Liposarcoma
Extraskeletal Ewing Sarcoma
Extraskeletal Myxoid Chondrosarcoma
Fibrosarcoma
Fibrosarcomatous Dermatofibrosarcoma Protuberans
Leiomyosarcoma
Malignant Peripheral Nerve Sheath Tumor
Myxofibrosarcoma
Pleomorphic Liposarcoma
Round Cell Sarcoma With EWSR1-non-ETS Fusion
Sarcoma
Soft Tissue Sarcoma
Soft Tissue Sarcoma of the Trunk and Extremities
Spindle Cell Sarcoma
Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Synovial Sarcoma
Undifferentiated Pleomorphic Sarcoma
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-07-30
Enrollment: 1582
Sex: ALL
Minimum age (years): 1
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This phase III trial compares chest computed tomography (CT) to chest x-ray (CXR) for lung surveillance after curative-intent resection of high-risk truncal-extremity soft tissue sarcoma. Currently, complete oncologic resection (with or without radiation therapy) is the standard of care for most high-risk soft tissue sarcoma that has not spread to other parts of the body (localized). However, despite curative-intent resection, 20-40% of patients will develop cancer that has spread from where it first started (primary site) to other places in the body (distant metastases), with the lungs being the most common site. Thus, lung surveillance is important for detection of lung metastases in order to facilitate timely treatment. Although there is general agreement about the usefulness of postoperative surveillance, consensus is lacking regarding the optimal modality for lung surveillance after curative-intent resection for high-risk soft tissue sarcoma. Current National Comprehensive Cancer Network guidelines recommend chest imaging with CT or CXR every 3-6 months for 2-3 years, then every 6 months for the next two years, and then annually after that for high-risk tumors. Data from across the United States and internationally indicate that there is considerable variation in clinical practice with regards to the use of CXR versus CT chest for lung surveillance. The information gained from this trial may allow researchers to determine the effectiveness of varying imaging modalities needed for optimal surveillance for patients with extremity or truncal soft tissue sarcoma.

Detailed description: PRIMARY OBJECTIVE:

I. To evaluate whether the use of chest x-ray (CXR) for lung metastasis surveillance for the first five years after resection of a truncal or extremity soft tissue sarcoma is comparable to the use of chest computed tomography (CT) in terms of overall survival.

SECONDARY OBJECTIVES:

I. To evaluate whether the use of CXR for lung metastasis surveillance for the first five years after resection of a truncal or extremity soft tissue sarcoma is comparable to the use of CT in terms of disease-free survival.

II. To assess the primary and secondary objectives in the pediatric and adolescent and young adult subpopulations.

III. To assess overall survival difference between arms based on specific histiotypes in subgroup analysis.

IV. Patient-reported outcomes and quality of life IVa. Fear of cancer; IVb. Anxiety; IVc. Overall quality of life; IVd. Financial burden; IVe. Patient-reported direct and indirect costs associated with care received.

IMAGING OBJECTIVES (EXPLORATORY):

I. To assess whether CT-derived and CXR-derived radiomic features can be used to determine whether a pulmonary nodule is benign or malignant (metastasis).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo CXR every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule undergo a CT and may undergo a biopsy on study.

ARM B: Patients undergo chest CT every 3 months for years 1-2, and every 6 months years 3-5. Patients with a suspicious or new nodule may undergo a biopsy on study.

Eligibility criteria: Inclusion Criteria:

* Patient must be ≥ 1 and ≤ 85 years old on the day of randomization
* Patient must have and undergone curative-intent (R0 or R1) resection of an American Joint Committee on Cancer (AJCC) 8th edition stage III truncal or extremity soft tissue sarcoma
* Patient must have a high-risk (grade 2 or 3) soft tissue carcinoma according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC)

  * Patients with the following histiotypes are eligible: dedifferentiated liposarcoma, pleomorphic liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, myxofibrosarcoma, fibrosarcomatous dermatofibrosarcoma protuberant variant, spindle cell sarcomas, pleomorphic sarcoma, fibrosarcoma,extra-skeletal myxoid chrondrosarcoma, extraskeletal Ewing and Ewing-like sarcoma, sarcoma not otherwise specified (NOS), or other grade 2 or grade 3 sarcomas not further classified
  * Patients with a high-risk histiotype that is typically not graded, including adult pleomorphic rhabdomyosarcoma, synovial sarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, alveolar soft part sarcoma, epithelioid sarcoma, or clear cell sarcoma are eligible
* Patient must have a tumor size ≥ 5 cm
* Patient must have had a R0 or R1 oncologic resection on final pathologic report
* Patient must have a baseline chest CT obtained within 30 days prior to randomization that is negative or detecting only non-suspicious nodules ≤ 4 mm
* Patients receiving preoperative or post-operative chemotherapy and/or radiotherapy for the primary tumor are eligible. However, all chemotherapy and/or radiotherapy must be completed prior to randomization
* Patient must not be pregnant due to the potential harmful risks associated with CXR and CT imaging to the unborn fetus

  * All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
  * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have a chest wall/upper truncal primary tumor requiring locoregional surveillance with CT or magnetic resonance imaging (MRI)
* Patient must not have retroperitoneal, mesenteric/abdominal sarcoma
* Patient must not have a primary bone sarcoma (including osteosarcomas, Ewings sarcoma, or chondrosarcomas), desmoid tumor, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, pediatric rhabdomyosarcoma, nor uterine sarcoma
* Patient must not have had a palliative or R2 resection
* Patient must not require routine cross-sectional imaging of the chest/lungs with CT/MRI/positron emission tomography (PET)
* Patient must not have participation in another clinical trial that is incompatible with this study surveillance schema and follow-up regimen
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Pediatric patients (\< 18 years of age) and patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. Child assent must be obtained as appropriate in accordance with institutional guidelines
* Patient must be English speaking to be eligible for the quality of life (QOL) component of the study

  * NOTE: Sites cannot translate the associated QOL forms

Primary outcomes:
measure: Overall survival (OS)
timeFrame: up to 5 years
Secondary outcomes:
measure: Lung disease-free survival
timeFrame: up to 5 years
measure: Overall survival (OS) in the pediatric and adolescent and young adult subpopulations
timeFrame: up to 5 years
measure: Lung disease-free survival in the pediatric and adolescent and young adult subpopulations
timeFrame: up to 5 years
measure: Overall Survival (OS) based on specific histiotypes
timeFrame: Up to 5 years of imaging protocol
measure: Fear of cancer as measured by a modified Psychological Consequences Questionnaire (PCQ):
timeFrame: baseline and every 6 month up to 5 years
measure: PROMIS Anxiety Score
timeFrame: baseline and every 6 month up to 5 years
measure: PROMIS Global-10, Global Health Overall Quality of Life
timeFrame: baseline and every 6 month up to 5 years
measure: Financial toxicity from the Comprehensive Score for Financial Toxicity (COST)
timeFrame: baseline and every 6 month up to 5 years
measure: Medical Expenditures Panel Surveys Reduction in material resources
timeFrame: baseline and every 6 month up to 5 years
measure: Care non-adherence
timeFrame: baseline and every 6 month up to 5 years
measure: Patient-reported out-of-pocket and indirect costs of care
timeFrame: baseline and every 6 month up to 5 years
Other outcomes:
measure: Radiomic features of pulmonary nodules
timeFrame: Up to 5 years of imaging protocol
Locations:
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Kenneth Cardona
role: PRINCIPAL_INVESTIGATOR
References: