Oropharyngeal Cancer
Conditions
Keywords
locally advanced, transorally resectable
Brief summary
Comparative Effectiveness Trial of Transoral Head and Neck Surgery followed by adjuvant Radio(chemo)therapy versus primary Radiochemotherapy for Oropharyngeal Cancer
Detailed description
This trial investigates the effectiveness of transoral head and neck surgery (TOS) for locally advanced, but transorally resectable oropharyngeal cancer followed by risk-adapted adjuvant therapy versus primary radiochemotherapy (definitive chemoradiotherapy, CRTX). Both treatments are internationally accepted standards. The choice of the treatment strategy depends on the preference of the responsible attending physician and on the country of residence. Internationally, mostly definitive chemoradiotherapy is regarded as the standard of care for oropharyngeal cancer. In Germany, however, transoral surgical resection is also well established and commonly practiced. The key question therefore is whether one of the two therapies is more effective than the other in clinical daily routine under the given conditions of our health care system and with a realistic, non-ideal patient cohort. For this reason, a comparative effectiveness research (CER) concept will be applied in this setting. The aim of this trial is primarily to show a superiority of the surgical approach in terms of local and locoregional control and secondarily to compare functional outcome and quality of life.
Interventions
PROCEDUREResection
Definitive surgery should generally be performed within 2 weeks, but not more than 4 weeks after randomization. The appropriately indicated neck dissection(s) may be performed either prior to, during the same session, or within 2 weeks after the resection of the primary tumor, but not later than 4 weeks following randomization. The primary tumor is to be resected with clear margins (R0) and en bloc in all cases. Frozen section assessment must be routinely and readily available.
RADIATIONRadiotherapy
6-7 weeks standard risk-adapted adjuvant radiotherapy 56-66 Gy, start within 6 weeks post-surgery Arm B: 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization, 70-72 Gy, SIB possible
DRUGChemotherapy
The investigational medicinal product (IMP) are the chemotherapeutical drugs Cisplatin, Mitomycin C and 5-FU. According to local routine, chemotherapy protocols as listed in study protocol should be used.
PROCEDURESalvage neck dissection
+/- Salvage neck dissection 12±2 weeks after treatment
Sponsors
Charite University, Berlin, Germany
University Medical Center Gießen and Marburg GmbH
University Hospital Ulm
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, two-arm, open label, multicenter, randomized, controlled comparative effectiveness study. The trial is based on an event-driven design: the final analysis will be performed when all events have been observed or the study was terminated at one of the interim analyses.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven SCC of the oropharynx; T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0, with only amendable to transoral resection) * Primary tumor must be resectable through transoral approach * p16 immunohistochemitry by local pathology or FFPE tissue must be available for central HPV diagnostic * Written and signed informed consent * Briefing through surgeon and radiation oncologist * ECOG PS ≥2, Karnofsky PS ≥ 60 % * Age ≥ 18 * Curative treatment intent * Adequate bone marrow function: leucocytes \> 3.0 x 109/L, neutrophils \> 1.5 x 109/L, platelets \> 80 x 109/L, hemoglobin \> 9.5 g/dL * Adequate liver function: Bilirubin \< 2.0 g/dL, SGOT, SGPT, \< 3 x ULN * If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing. * dental examination and appropriate dental therapy if needed prior to Confidential TopROC 2017\_03\_24 Version 1.0 Seite 15 von 124 beginning of radiotherapy * Nutritional evaluation prior to initiation of therapy and optional prophylactic gastrostomy (PEG) tube placement
Exclusion criteria
* Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix * Unknown primary (CUP), nasopharynx, hypopharynx, laryngeal or salivary gland cancer * Metastatic disease * Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C * Hemoglobin level \<9.5g/dl within 4 weeks before randomization * Pregnancy or lactation * Women of child-bearing potential with unclear contraception * Previous treatment with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck * Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening * Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol * Patients institutionalized by official means or court order * Deficient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to local or locoregional failure or death from any cause | Defined as time from randomization up to 36 month | The primary objective of this study is to evaluate the effectiveness of primary surgical versus non-surgical treatment of patients with locally advanced, but transorally resectable oropharyngeal cancer in terms of time to local or locoregional failure or death from any cause (LRF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Until 3 years after randomization | Overall survival (OS) in both study arms, follow-up visits until the end of study |
| Disease-free survival | Until 3 years after randomization | Disease-free survival (DFS) in both study arms. CT- Scans will be performed at month 3, month 6, 18, 30 and in case of suspicion of recurrence |
| Effectiveness in terms of toxicity | Until 3 years after randomization | Effectiveness in terms of toxicity in both study arms. Monitoring of AE's/SAE's from randomization to 28 days after the last administration of IMP and/or 5 months after randomization in this trial |
| Quality of life evaluated by patient | Until 3 years after randomization | Quality of life Questionnaires using QLQ H&N-43 in both study arms |
| Cost-utility | Until 3 years after randomization | Cost-utility in both study armsusing Questionnaire Health Care Utilization and Productivity loss. |
| Cost-effectiveness | Until 3 years after randomization | Cost-effectiveness in both study arms using Questionnaire Health Utilization and Productivity loss. |
| Effectiveness in terms of morbidity | Until 3 years after randomization | Effectiveness in terms of morbidity (including swallowing function by MDADI Score) by late morbidity documentation in both study arms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tertiary objectives include comparisons of treatment effects between HPV- Status | Up to 36 month | Subgroup analysis of HPV-positive and HPV-negative oropharynx carcinoma |
Countries
Germany
Outcome results
None listed