Phage II Trial of Stathmin as Predictive Biomarker for TPF Induction Chemotherapy in OSCC
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|ClinicalTrials.gov Identifier: NCT03326947|
Recruitment Status : Recruiting
First Posted : October 31, 2017
Last Update Posted : January 13, 2020
|First Submitted Date ICMJE||August 16, 2017|
|First Posted Date ICMJE||October 31, 2017|
|Last Update Posted Date||January 13, 2020|
|Actual Study Start Date ICMJE||January 1, 2018|
|Estimated Primary Completion Date||January 1, 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Overall survival [ Time Frame: 12 weeks. ]
Overall survival was calculated from the date of randomization to death from any cause
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
||Disease free survival [ Time Frame: 12 weeks. ]
Disease free survival was calculated from the date of randomization to recurrence, locoregional recurrence, or death from any cause
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Phage II Trial of Stathmin as Predictive Biomarker for TPF Induction Chemotherapy in OSCC|
|Official Title ICMJE||A Randomized Phase II Trial of Low Stathmin Expression as a Predictive Biomarker for OSCC Patients Receiving TPF Induction Chemotherapy Followed by Radical Surgery and Radiotherapy/Chemoradiotherapy|
|Brief Summary||To investigate the predictive value of stathmin expression as a predictive biomarker in OSCC patients, who treated with TPF (docetaxel, cisplatin and 5-fluorouracil ) induction chemotherapy followed by radical surgery and radiotherapy/chemoradiotherapy.|
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 subgroup analysis proves that the induction chemotherapy of TPF protocol could benefit the patients with low stathmin expression.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 OSCC patients with low stathmin expression. 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 5-year survival rate of 93% in the experiment group and 52% 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 5 years, and 10% of patients would drop out early or be lost to follow-up. A total number of 60 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/chemoradiotherapy. 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.
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 of 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
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Neoplasm Neck|
|Intervention ICMJE||Drug: docetaxel, cisplatin and 5-fluorouracil
Drug: TPF induction chemotherapy TPF induction chemotherapy: 2 cycles; docetaxel(75mg/m^2), cisplatin(75 mg/m^2), 5-Fu(750 mg/m^2/day) for 5 days; 16 days later, the 2nd cycle. 2 weeks later, surgery.
Surgery: radical resection and full neck dissection with reconstruction. Radiotherapy: 4-6 weeks after surgery, 1.8-2Gy/day, 5 days/week for 6 weeks, and totally 54-60Gy, for high risk factors, concurrent chemotherapy with cisplatin of 80mg/m2.
TPF protocol group Procedure/Surgery: surgery In the TPF group,surgery was performed at least 2 weeks after completion of induction chemotherapy.Surgery group includes radical resection of the primary lesion and full neck dissection(functional or radical) with proper reconstruction(pedicle or free flap) were performed.
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||January 1, 2024|
|Estimated Primary Completion Date||January 1, 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Pathological diagnosis of squamous cell carcinoma of the oral cavity (tongue, gingiva, buccal mucosa, floor of mouth, palate, and retromolar region).
Age: 18 to 75 years old. Sex: both males and females. Karnofsky performance status (KPS) >70. Low grade of Stathmin 1 expression by immunohistochemistry. Clinical stage III/IVA. White blood cell >3,000/mm3, hemoglobin>8g/L, platelet count>80,000/mm3. Hepatic function: ALAT(alanine aminotransferase )/ASAT(aspartate transaminase ) <2.5 times the upper limit of normal (ULN), bilirubin <1.5 times ULN.
Serum creatinine <1.5 times ULN. Written informed consent
Distant metastatic disease and other cancers. Previous surgical procedure of the primary tumors or lymph nodes (except diagnostic biopsy).
Previous radiotherapy or chemotherapy. Other previous malignancies within 5 years. Sever systematic diseases such as severe pulmonary or cardiac diseases. Legal incapacity or limited legal capacity. Creatinine clearance <30ml/min. Pregnancy (confirmed by serum or urine β-HCG) or lactation period
|Ages ICMJE||18 Years to 75 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||China|
|Removed Location Countries|
|NCT Number ICMJE||NCT03326947|
|Other Study ID Numbers ICMJE||Stathmin for TPF in OSCC|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Lai-ping Zhong, Shanghai Jiao Tong University School of Medicine|
|Study Sponsor ICMJE||Shanghai Jiao Tong University School of Medicine|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||Shanghai Jiao Tong University School of Medicine|
|Verification Date||January 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP