Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02285543 |
| Other study ID # |
TOPIC |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2016 |
| Est. completion date |
July 30, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Shanghai Jiao Tong University School of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To confirm the subgroup result from TPF (docetaxel, cisplatin and 5-fluorouracil ) trial
(NCT01542931) that cN2 OSCC patients could benefit from TPF induction chemotherapy compared
to the standard treatment.
Description:
Induction chemotherapy is regarded as an effective way to reduce or downgrade the locally
advanced or aggressive cancers, and to improve the chance of eradication of the locoregional
lesions by radical surgery and/or radiotherapy. However, there are still debates on the
clinical value of induction chemotherapy for patients with advanced and resectable oral
squamous cell carcinoma(OSCC). A prospective, open label, parallel, interventional,
randomized control trial on TPF induction chemotherapy indicate there is no difference in
overall survival, disease free survival, local regional recurrence free survival and
metastasis free survival between experimental group and control group,（Zhong et al,
Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and
Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral
Squamous Cell Carcinoma, J Clin Oncol 2013） however, the meta analysis proves that the
induction chemotherapy of TPF protocol could benefit the patients with cN2 locally advanced
oral squamous cell carcinoma. The previous study was registered at ClinicalTrials.gov website
with NCT01542931 identification number.
This prospective, interventional, randomized control trial was to evaluate the TPF induction
chemotherapy have a better effects in the cN2 patients with locally advanced and resectable
OSCC. The patients would receive TPF induction chemotherapy followed by radical surgery and
post-operative radiotherapy (the experimental group) or radical surgery and post-operative
radiotherapy (the control group).
The study had a power of 80% on the basis of an assumed 2-year survival rate of 62.4% in the
experiment group and 36.9% in the control group, with use of a two-sided log-rank test at a
level of significance of 0.05. The recruitment period would be 2 years, and the follow-up
period would be 2 years, and 15% of patients would drop out early or be lost to follow-up. A
total number of 101 patients were to be recruited with stplan 4.5 software calculation.
（Department of Biostatics, MD Anderson Cancer Center, University of Texas，USA） The patients
in the experimental group received the TPF induction chemotherapy for 2 cycles followed by
radical surgery and post-operative radiotherapy. The palpable edges of the primary lesion
(both the longest and shortest axis) were marked before induction chemotherapy by at least
four points, which were 0.5cm away. The patients in the control group received the radical
surgery and post-operative radiotherapy/chemoradiotherapy.
Induction chemotherapy: For the patients who were randomly assigned to receive TPF induction
chemotherapy, peripherally inserted central catheter was firstly inserted before intravenous
infusion, docetaxel(at a dose of 75mg/m2 of body surface area) was administered as a 2-hour
intravenous infusion, followed by intravenous cisplatin(75 mg/m2), administered during a
period of 2 to 3 hours. Then, 5-Fu(750 mg/m2/day) was administered as a 120-hour continuous
intravenous infusion for 5 days. Induction chemotherapy was given every 3 weeks for 2 cycles,
unless there was disease progression, unacceptable toxic effects, or withdrawal of consent by
the patients. Dexamethasone was given before docetaxel infusion to prevent docetaxel-related
hypersensitivity reactions, skin toxic effects, and fluid retention; prophylactic antibiotics
were also given starting on day 5 of each cycle for 3 days. Hydration with diuretic and
antiemetic treatment was also performed. Primary prophylaxis with recombinant granulocyte
colony-stimulating factor was not suggested. Chemotherapy dose reductions were allowed for
grade 3/4 toxicities occurring after cycle 1: 25% and 50% dose reductions of the three
chemotherapy agents were suggested for grade 3 and grade 4 hematologic toxicities or
gastrointestinal toxicities, respectively; 25% and 50% cisplatin dose reductions were
suggested for grade 3 and grade 4 renal toxicities, respectively. Surgery was performed at
least 2 weeks after completion of induction chemotherapy.
Surgery: Radical resection of the primary lesion and full neck dissection(functional or
radical) with proper reconstruction(pedicle or free flap) were performed. The safety margins
of the primary lesion were 1.0-1.5cm far away from the palpable margins of the lesion; for
patients who received induction chemotherapy, the safety margins were 1.0cm away from the
marks that were placed before induction chemotherapy, to ensure the same extent surgery in
both arms. Frozen sections during surgery were performed to confirm adequate margins.
Post-operative radiotherapy: Radiotherapy was arranged 4 to 6 weeks after surgery. Routine
external beam radiotherapy, such as conformal or intensity modulated radiotherapy was
performed, and the dose was 1.8-2 Gy/day, 5 days/week for 6 weeks, and totally 54-60 Gy, in
the patient with high risk features, such as positive surgical margin, extra capsular nodal
spread, vascular embolism, concurrent chemotherapy with cisplatin 80mg/m2 was suggested.
A complete medical history was obtained and tumor assessment was performed at baseline.
Clinical tumor response was assessed by clinical evaluation and imaging study and was
characterized according to the criteria of response evaluation criteria in solid tumors
(version 1.1) before surgery. Post-operative pathologic response was assessed by
post-operative pathologic examination as good and bad response. A good response was defined
as absence of any tumor cells (pathologic complete response) or presence of scattered foci of
a few tumor cells (minimal residual disease with <10% viable tumor cells); otherwise, a bad
pathologic response was defined. Toxic effects were assessed weekly during and after
completion of induction chemotherapy and radiotherapy according to the common terminology
criteria for adverse events (version 3.0).
Overall survival was calculated from the date of randomization to the date of death; disease
free survival was calculated from the date of randomization to tumor recurrence or distant
metastasis or death from any cause; locoregional recurrence/distant metastasis free survival
was calculated from the date of randomization to locoregional recurrence/distant metastasis
of tumor or death from any cause. Time to locoregional recurrence/distant metastasis was
calculated from the date of finishing treatment to tumor locoregional recurrence/distant
metastasis. Patients were monitored by every three months in the first two years, every six
months in the next 2 years, and once a year thereafter until death or data censoring.
