Ignite Creation Date:
2025-12-24 @ 5:58 PM
Ignite Modification Date:
2026-02-25 @ 6:35 PM
Study NCT ID:
NCT02655068
Status:
TERMINATED
Last Update Posted:
2017-07-31
First Post:
2015-12-01
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase III Trial of PET/CT vs. CTSurveilance for Head and Neck Cancer
Sponsor:
University of Pittsburgh
Organization:
Study Overview
Official Title:
Efficacy of Monitoring Strategies Following Definitive Therapy for Locally Advanced Head and Neck Cancer: A Randomized, Phase III Trial of PET/CT vs. CT Surveillance
Status:
TERMINATED
Status Verified Date:
2017-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
due to non-feasibility
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The null hypothesis is that patients screened by PET/CT will not have detection of disease recurrence any earlier than those screened by CT alone. The alternative hypothesis is that PET/CT surveillance will lead to detection of disease recurrence 3 months earlier than CT surveillance. Furthermore, to reject the null hypothesis, earlier detection must be associated with a cause-specific survival improvement of 10%. Primary endpoints will include time from the completion of definitive therapy to diagnosis of recurrent disease, and absolute survival within 3 years after completion of initial therapy. Duration of survival between diagnosis of recurrence and subsequent death will not be a primary endpoint because the investigators expect that PET/CT will offer an opportunity for earlier recognition of recurrence and be subject to lead-time bias. Duration of survival will be measured from completion of primary treatment until death. Note: the presence of residual disease at surgical consolidation does not constitute a recurrence event.
Detailed Description:
Head and neck cancer (HNC) is the sixth leading incident cancer worldwide with 600,000 cases expected in 2012.1 The vast majority of cases are head and neck squamous cell carcinoma (HNSCC), comprising \> 90% of histologies. Despite advances in multimodality therapy for HNSCC, 5-year overall survival (OS) is 40-60%, and has increased only incrementally in the past two decades.2 Improved prognosis is largely attributable to the emerging epidemic of oral human papillomavirus infection (HPV). An increasing proportion of oropharyngeal HNC is driven by oncogenic HPV, rather than the classic risk factors of tobacco and alcohol; HPV etiology is associated with improved survival after conventional treatments.3,4 Most patients with HNC present with locally advanced disease (stage III-IVb), and have associated anatomic deformity due to the primary tumor or neck adenopathy. Intensive multi-modality therapy including surgery, chemotherapy, and radiotherapy is routinely required. The current standard of care for primary nonsurgical management of previously untreated locally advanced (PULA) HNSCC is concurrent cisplatin-radiotherapy (RT), as administered in the sentinel Intergroup trial 0126 5,6. Likewise, the standard of care in the adjuvant management of high risk disease is cisplatin-RT as proven in the Radiation Therapy Oncology Group (RTOG) 95-01 and European Organization for Research and Treatment of Cancer (EORTC) 22931 trials.7,8 Despite curative-intent surgical or non-surgical therapy, approximately half of people will relapse. Unlike most other epithelial malignancies, the dominant pattern of relapse and the driver of HNC-related mortality is locoregional recurrence.9 The vast majority of recurrences occur within the first two years following definitive therapy.
Patient evaluation following completion of definitive therapy for HNC is confounded by anatomic deformity which began with the primary tumor and nodal metastatic disease, and is further compounded by treatment-related effects such as scarring, flap reconstruction, and edema. There currently does not exist an ideal method for surveillance. National Comprehensive Cancer Center Network (NCCN) guidelines call for physical examination and intermittent imaging as required. Clinical trial designs incorporating definitive chemoradiotherapy typically employ a diagnostic, contrast-enhanced CT of the neck every 3 months for 1 year, followed by every 6 months for 1 year, followed by annual evaluations (eg. ECOG 1308; UPCI 07-021). Single-arm prospective studies have suggested that positron emission tomography (PET) with fluorodeoxyglucose (FDG) is more sensitive than CT or physical examination alone for residual or recurrent disease, particularly when conducted with integrated diagnostic CT scan. In these studies, negative PET/CT scans correlated with lower likelihood of residual nodal pathology and improved DFS.12,13 The current practice at the University of Pittsburgh is to employ PET/CT surveillance, in particular following definitive chemoradiotherapy. However, prior investigations have not demonstrated improved salvage or survival outcomes with use of PET/CT surveillance, which is clearly more costly than CT surveillance and may carry morbidity related to increased diagnostic procedures for false-positive findings.
The investigators propose a prospective, randomized phase III trial in patients undergoing definitive therapy for locally advanced Stage III-IVb carcinoma involving the head and neck. This includes primary tumors of the oral cavity, pharynx, and larynx, as well as cancer of the salivary glands and squamous cell carcinoma of the skin. Patients who have realized a clinical complete response to definitive therapy will be randomized to PET/CT vs. CT surveillance, to test the hypothesis that PET/CT surveillance is superior to CT surveillance due to earlier diagnosis of recurrence, more timely and effective salvage, and consequent reduction in HNC mortality. The study intervention will solely be the imaging modality assigned for surveillance. All study patients will otherwise be monitored strictly according to NCCN guidelines, including history and physical examination (and endoscopy where appropriate). Assigned imaging will be conducted at identical intervals. Areas suspicious for recurrence on the basis of history and physical examination, endoscopy or imaging will be biopsied. Therapeutic interventions will be determined by the treatment team, which will include at least one member from medical oncology, radiation oncology, and otolaryngology/head and neck surgery. Patients with recurrent locoregional disease will be offered salvage treatment as indicated by the clinical situation.
Patient evaluation following completion of definitive therapy for HNC is confounded by anatomic deformity which began with the primary tumor and nodal metastatic disease, and is further compounded by treatment-related effects such as scarring, flap reconstruction, and edema. There currently does not exist an ideal method for surveillance. National Comprehensive Cancer Center Network (NCCN) guidelines call for physical examination and intermittent imaging as required. Clinical trial designs incorporating definitive chemoradiotherapy typically employ a diagnostic, contrast-enhanced CT of the neck every 3 months for 1 year, followed by every 6 months for 1 year, followed by annual evaluations (eg. ECOG 1308; UPCI 07-021). Single-arm prospective studies have suggested that positron emission tomography (PET) with fluorodeoxyglucose (FDG) is more sensitive than CT or physical examination alone for residual or recurrent disease, particularly when conducted with integrated diagnostic CT scan. In these studies, negative PET/CT scans correlated with lower likelihood of residual nodal pathology and improved DFS.12,13 The current practice at the University of Pittsburgh is to employ PET/CT surveillance, in particular following definitive chemoradiotherapy. However, prior investigations have not demonstrated improved salvage or survival outcomes with use of PET/CT surveillance, which is clearly more costly than CT surveillance and may carry morbidity related to increased diagnostic procedures for false-positive findings.
The investigators propose a prospective, randomized phase III trial in patients undergoing definitive therapy for locally advanced Stage III-IVb carcinoma involving the head and neck. This includes primary tumors of the oral cavity, pharynx, and larynx, as well as cancer of the salivary glands and squamous cell carcinoma of the skin. Patients who have realized a clinical complete response to definitive therapy will be randomized to PET/CT vs. CT surveillance, to test the hypothesis that PET/CT surveillance is superior to CT surveillance due to earlier diagnosis of recurrence, more timely and effective salvage, and consequent reduction in HNC mortality. The study intervention will solely be the imaging modality assigned for surveillance. All study patients will otherwise be monitored strictly according to NCCN guidelines, including history and physical examination (and endoscopy where appropriate). Assigned imaging will be conducted at identical intervals. Areas suspicious for recurrence on the basis of history and physical examination, endoscopy or imaging will be biopsied. Therapeutic interventions will be determined by the treatment team, which will include at least one member from medical oncology, radiation oncology, and otolaryngology/head and neck surgery. Patients with recurrent locoregional disease will be offered salvage treatment as indicated by the clinical situation.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: