Neoadjuvant Chemotherapy Followed by Preoperative Chemoradiation in Resectable Squamous-cell Esophageal Cancer

Phase 2

• Conditions: Esophageal Neoplasms; Concurrent Chemoradiotherapy; Squamous Cell Carcinoma
• Interventions: Drug: Paclitaxel; Drug: Cisplatin; Drug: Fluorouracil; Radiation: chemoradiotherapy; Procedure: Ivor Lewis esophagogastrectomy

• Registration Number: NCT03579004
• Lead Sponsor: Mona Frolova

Brief Summary

This study is conducted to evaluate efficacy and safety of neoadjuvant chemotherapy followed by preoperative chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma

Detailed Description

This study is conducted to evaluate efficacy and safety of neoadjuvant chemotherapy followed by preoperative chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma.

Patients with resectable esophageal squamous cell carcinoma receive 2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). Patients who do not progress with distant metastases start preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gy for 4 weeks).

4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy irrespectively of objective response.

Study Timeline

• Study Start: 2017-07-10
• Study First Submitted: 2018-06-12
• Status Verified: 2018-07
• Study First Submitted QC: 2018-07-04
• Last Update Submitted: 2018-07-04
• Study First Posted: 2018-07-06
• Last Update Posted: 2018-07-06
• Primary Completion: 2020-07-10
• Study Completion: 2020-07-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. age 18-75

2. Histologically or cytologically confirmed resectable squamous-cell Tumor (T)1-2 node (N)+, T3N0-3 esophageal cancer. Inclusion of patients with morphologically confirmed and potentially resectable supraclavicular lymphnodes (unilateral, less than 1,5 cm in short axis) is allowed

3. No prior antineoplastic treatment

4. Eastern Cooperative Oncology Group (ECOG) status 0-2

5. Adequate organ function, evidenced by laboratory results with no contraindications to chemotherapy

   • absolute neutrophil count ≥ 1,500 х109/l
   • thrombocytes ≥ 100 х 109/l
   • hemoglobin ≥ 90 mg/l
   • creatinine < 115 µmol/л or creatinine clearance ≥ 55 ml/min
   • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN)
   • alkaline phosphatase (ALP) > 5 x ULN
   • bilirubin > 1,5 х ULN

6. Women of childbearing potential must have negative pregnancy test, performed 7 days prior to initial treatment

7. Patients must follow appropriate contraception rules during whole treatment period

8. Decrease of body weight must not be more than 20% in last 6 months

Exclusion Criteria

1. Presence of distant metastases except for metastatic supraclavicular lymphnodes;
2. Bulky (>3 cm) regional lymphnodes metastases;
3. Cervical esophageal cancer;
4. Presence of tumor fistula;
5. Prior malignant tumor, except for proper treated skin basal cell carcinoma and in situ cervical cancer;
6. Active infectious diseases and concomitant diseases that can affect treatment tolerability, surgery and other study procedures;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trimodality approach	Cisplatin	2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy.
Trimodality approach	chemoradiotherapy	2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy.
Trimodality approach	Ivor Lewis esophagogastrectomy	2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy.
Trimodality approach	Paclitaxel	2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy.
Trimodality approach	Fluorouracil	2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy.

Primary Outcome Measures

Name	Time	Method
Disease free survival	24 months	Disease free survival will be calculated from the start of the treatment to the disease progression or death of any reason.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0	24 months	Toxicity will be assessed separately after chemotherapy, chemoradiotherapy and surgery according NCI CTC AE 4.0
Objective response rate according to RECIST 1.1	24 months	Objective response rate will be evaluated separately after chemotherapy and chemoradiotherapy.
Overall survival	24 months	Overall survival will be calculated from the start of the treatment to the death of any reason.
Pathological complete response rate following chemoradiotherapy	24 months	Pathological complete response rate following chemoradiotherapy will be assessed in resected patients

Trial Locations

Locations (2)

Russian Cancer Research Center named after N.N.Blokhin RAMS; 🇷🇺 Moscow, Russian Federation

Alexey Tryakin; 🇷🇺 Moscow, Russian Federation