Clinical trial NCT02976909: Efficacy and Safety of TPF Induction Chemotherapy for Borderline-resectable Esophageal Squamous Cell Carcinoma
Official title: Paclitaxel In Combination With Cisplatin and 5-fluorouracil(TPF) Induction Chemotherapy for Locally Advanced Borderline-resectable Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-11-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial studies the efficacy and safty of paclitaxel in combination with cisplatin and 5-fluorouracil(TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma.

Detailed description: Esophageal cancer is one of the most common malignant tumors in China. In Asian countries, esophageal squamous carcinoma is the main pathological type of esophageal carcinoma. Prognosis of esophageal squamous carcinoma is usually poor and surgery is the only radical treatment. However, the optimal therapy pattern for local advanced esophageal carcinoma is still unclear. Part of the patients that clinical staging as T4 and with bulky lymph node metastasis are initially diagnosed as borderline-resectable, which means patients may be able to undergo R0 resection. However, for patients who are diagnosed as borderline-resectable esophageal carcinoma, there are still no sufficient studies implicate that how to improve R0 resection rate by convertion chemotherapy. Cisplatin in combination with 5-FU and docetaxel regimen(DCF) was reported as effective neoadjuvant chemotherapy in treating esophageal squamous carcinoma. However, studies also showed that the DCF regimen caused severe adverse reaction. The mechanism of paclitaxel is similar to docetaxel while with less adverse events than docetaxel. Based on the research situation mentioned above, the investigators decided to conduct a phase II clinical trial to further explore the efficacy and safety of paclitaxel in combination with cisplatin and 5-FU (TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous carcinoma.

Eligibility criteria: Inclusion Criteria:

1. Patients should be voluntary to the trial and provide with signed informed consent.
2. Male or female patients, age:18-70 years old
3. Confirmed by histology of thoracic esophageal squamous cell carcinoma without metastasis and diagnosed as boundary resectable by Multidisciplinary consultation, including cT4 and/or bulky lymphadenopathy that may invade nearby organs(such as the great vessels, trachea and heart, etc.)
4. Measurable or unmeasurable lesions according the RECIST 1.1 criteria.
5. No previous chemotherapy or radiotherapy.
6. Life expectancy ≥ 3 months.
7. ECOG PS 0-1.
8. Blood routine within 7 days：Hb ≥9g/L，NE ≥1.5×109/L，PLT ≥100×109/L；
9. Hepatic and renal function：TB \<1.5 UNL， Cr\< 1.5× UNL， AST / ALT \< 2.5× UNL， ALP \< 5.0 × UNL。
10. No severe complications such as active digestive tract hemorrhage, perforation, jaundice, gastrointestinal obstruction, non-cancerous fever \> 38 ℃
11. Fertile patients should take effective contraceptive measures.
12. Patients should have good compliance and cooperate with the evaluation of efficacy and adverse events and follow-ups according to the research plan.

Exclusion Criteria:

1. Cervical esophageal carcinoma.
2. Known severe hypersensitivity to drugs in the regimen.
3. Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment(with the exception of nonmelanoma skin cancer or cervical carcinoma in situ).
4. Evidence of serious heart disease, including recorded history of congestive heart-failure, uncontrolled serious arrhythmia, angina that needs treatment of drugs, clinical diagnosed cardiac valve disease, history of serious myocardial infarction and intractable hypertension.
5. Evidence of chronic diarrhea(≥4 times/day) or renal dysfunction.
6. Evidence of active infection or active epidemic disease.
7. Psychiatric illness that would prevent the patient from giving informed consent
8. Pregnant or lactating women.

Primary outcomes:
measure: R0 resection rate
timeFrame: following resection for up to 36 months
Secondary outcomes:
measure: pathologic complete response rate
timeFrame: following resection for up to 36 months
measure: OS
timeFrame: for up to 36 months
measure: PFS
timeFrame: for up to 36 months
measure: Adverse envents
timeFrame: for up to 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yu-hong Li, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Z, Hu M, Hu Y, Li Q, Wu J, Fong WP, Ren C, Wang D, Tan Q, Yang H, Li Y. Paclitaxel plus cisplatin and 5-fluorouracil induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: a phase II clinical trial. Esophagus. 2022 Jan;19(1):120-128. doi: 10.1007/s10388-021-00864-8. Epub 2021 Jul 28.