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Comparing Paclitaxel/Cisplatin and Cisplatin/5-fluorouracil in Neo-CRT for ESCC

Primary Purpose

Esophageal Squamous Cell Carcinoma, Chemoradiation

Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
neoadjuvant chemoradiation
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Pathologically proven squamous cell carcinoma of the intrathoracic esophagus.
  2. Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography:

    A. T3/4a, N0, M0; B. T1-3, N1-3, M0;

  3. Tumor length longitudinal ≤ 8cm and radial ≤ 5cm.
  4. The tumor must not extend more than 2cm into the stomach.
  5. The tumor must not involve cervical esophagus.
  6. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
  7. Age ≥ 20 and ≤ 75 years old.
  8. Performance status ECOG 0~2.
  9. Adequate bone marrow reserves, defined as:

    A. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; B. platelets ≥ 100,000/µl.

  10. Adequate liver function reserves, defined as:

    A. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); B. serum total bilirubin ≤ 2.0 x upper limit of normal (ULN).

  11. Adequate renal function: Creatinine ≤1.5 x upper normal limit or estimated creatinine clearance ≥ 50 ml/min (estimated by Cockcroft-Gault formulation)
  12. Written informed consent.
  13. Patients must be able to fill in quality of life questionnaires.

Exclusion Criteria:

  1. Adenocarcinoma.
  2. Previous thoracic irradiation.
  3. Previous systemic chemotherapy
  4. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer.
  5. Prior malignancy, except for the following:

    A. adequately treated basal cell or squamous cell skin cancer; B. in-situ cervical cancer; C. a "cured" malignancy more than 5 years prior to enrollment.

  6. Significant co-morbid disease, which prohibits the conduction of chemotherapy, concurrent chemo- radiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders.
  7. Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication. Patients with a history of 2nd or 3rd degree heart block.
  8. Pre-existing motor or sensory neurotoxicity greater than grade 1.
  9. Patients with prior allergic reactions to drug containing Cremophor, such as teniposide or cyclosporine.
  10. Weight loss > 15%.
  11. Dementia or altered mental status that would prohibit the understanding and completion of informed consent and questionnaires.
  12. Estimated life expectancy less than 3 months.

Sites / Locations

  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

paclitaxel plus cisplatin

cisplatin plus 5-fluorouracil

Arm Description

A. T: Paclitaxel 50 mg/m2, 1h IVF, weekly, week 1 to week 5 during CRT. B. P: Cisplatin 30 mg/m2, 2 h IVF, weekly following paclitaxel, week 1 to week 5 during CRT.

A. P: Cisplatin 75 mg/m2, 2 h IVF, on day 1 of week 1 and week 5 during CRT. B. F: 5-FU 1,000 mg/m2, 24 h IVF, on day 1, 2, 3, 4 of week 1 and week 5 during CRT.

Outcomes

Primary Outcome Measures

pathological complete response
No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists

Secondary Outcome Measures

Overall survival
Time from enrollment to death
disease free survival
From the day of surgery with R0 resection to recurrence or death of any reasons
clinical response
The clinical response evaluation for the effect of neoadjuvant CRT will be done around 3±1 weeks after completing CRT. Evaluation will be performed with panendoscopy, EUS, CT, and PET. Clinical responses assessment will include: Overall clinical response according to RECIST1.1 and Japanese Esophageal Society (JES) Endoscopic response criteria according to JES Metabolic response evaluated by PET
operation rate
The ratio of the number of patients who receive surgery over the number of patients enrolled
R0 resection rate
The ratio of the number of patients with surgical R0 resection over the number of patients who receive surgery
tumor regression grade
A 4-tiered tumor regression grading (TRG) system will be used according to the extent of residual carcinoma in the whole tumor area of the esophageal specimen. TRG 1: no residual carcinoma. TRG 2: 1%- 10% residual carcinoma. TRG 3: 11%- 50% residual carcinoma. TRG 4: >50% residual carcinoma
The total score of participants of both arms will be analyzed and compared.
By World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Taiwan version (2005), quality of life will be assessed at enrollment, at the end of neoadjuvant CRT, and 3 months after surgery. There are 28 subscales in the questionnaire. Each subscale has 5 scores from 1 (the worst) to 5 (the best). The scores of each subscale are summed to be a total score.
Number of participants with treatment-related adverse events as assessed by the NCI Common Toxicity Criteria (CTC)
By the NCI Common Toxicity Criteria (CTC), version 4.0., number of participants with treatment-related adverse events, all grades and grade 3/4, will be assessed.

Full Information

First Posted
June 27, 2017
Last Updated
June 5, 2022
Sponsor
National Taiwan University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03623737
Brief Title
Comparing Paclitaxel/Cisplatin and Cisplatin/5-fluorouracil in Neo-CRT for ESCC
Official Title
A Randomized Phase II/III Study of Paclitaxel/Cisplatin Versus Cisplatin/5-fluorouracil in Neoadjuvant Chemoradiation Followed by Surgery for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This clinical trial has two stages: phase II and phase III. Eligible patients will be randomized 1:1 to the two arms: paclitaxel plus cisplatin and cisplatin plus 5-fluorouracil. The phase II stage will enroll 128 patients, 64 patients for each arm. The endpoint of the phase II stage is complete pathological response (pCR). If the endpoint, i.e., the significant improvement of pCR rate, is met, the clinical trial will proceed to the phase III stage, in which 120 more patients will be enrolled. The estimated enrollment time is four years with 3 more years of follow-up after completing enrollment. The primary endpoint of the clinical trial is overall survival, and the secondary endpoints include clinical response, disease free survival, operation rate, complete resection rate, tumor regression rate, hospital stay days after surgery, safety and toxicity, and quality of life.
Detailed Description
Stage 1: Neoadjuvant chemoradiation (CRT): Stage 2: Evaluation of clinical responses Evaluation will be done at 3±1 weeks after completing the last fraction of radiotherapy. Evaluation will be performed with panendoscopy, endoscopic ultrasonography (EUS), computed tomography (CT), and positron emission tomography (PET). Stage 3: Surgery Patients will receive esophagectomy with two field lymph node dissection unless: A. Patients become medically unfit for surgery. B. Tumor becomes metastatic or unresectable. C. Patients refuse surgery. Patients who do not receive surgery will go on a second section of CRT: A. Radiation: 180cGy/fraction, once daily, 5 days a week, up to a total of 6,300cGy. B. Arm A: i. T: Paclitaxel 50 mg/m2, 1h IVF, weekly, week 1 to week 3 during CRT. ii. P: Cisplatin 30 mg/m2, 2 h IVF, weekly following paclitaxel, week 1 to week 3 during CRT. C. Arm B: i. P: Cisplatin 75 mg/m2, 2 h IVF, on day 1 of week 1 during CRT. ii. F: 5-FU 1,000 mg/m2, 24 h IVF, on day 1, 2, 3, 4 of week 1 during CRT. Patients, who receive surgery with R2 resection or the pathology showing positive margins or extracapsular invasion of regional lymph nodes, will also receive the second section of CRT described in above-mentioned stage 3-2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Chemoradiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
248 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
paclitaxel plus cisplatin
Arm Type
Experimental
Arm Description
A. T: Paclitaxel 50 mg/m2, 1h IVF, weekly, week 1 to week 5 during CRT. B. P: Cisplatin 30 mg/m2, 2 h IVF, weekly following paclitaxel, week 1 to week 5 during CRT.
Arm Title
cisplatin plus 5-fluorouracil
Arm Type
Active Comparator
Arm Description
A. P: Cisplatin 75 mg/m2, 2 h IVF, on day 1 of week 1 and week 5 during CRT. B. F: 5-FU 1,000 mg/m2, 24 h IVF, on day 1, 2, 3, 4 of week 1 and week 5 during CRT.
Intervention Type
Drug
Intervention Name(s)
neoadjuvant chemoradiation
Other Intervention Name(s)
esophagectomy
Intervention Description
Neoadjuvant chemoradiation: Radiation: 180cGy/fraction, once daily, 5 days a week, to a total of 4,500cGy. Chemotherapy: Arm A or Arm B Surgery: esophagectomy and 3-fields lymph node dissection
Primary Outcome Measure Information:
Title
pathological complete response
Description
No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Time from enrollment to death
Time Frame
4 years
Title
disease free survival
Description
From the day of surgery with R0 resection to recurrence or death of any reasons
Time Frame
4 years
Title
clinical response
Description
The clinical response evaluation for the effect of neoadjuvant CRT will be done around 3±1 weeks after completing CRT. Evaluation will be performed with panendoscopy, EUS, CT, and PET. Clinical responses assessment will include: Overall clinical response according to RECIST1.1 and Japanese Esophageal Society (JES) Endoscopic response criteria according to JES Metabolic response evaluated by PET
Time Frame
2 years
Title
operation rate
Description
The ratio of the number of patients who receive surgery over the number of patients enrolled
Time Frame
2 years
Title
R0 resection rate
Description
The ratio of the number of patients with surgical R0 resection over the number of patients who receive surgery
Time Frame
2 years
Title
tumor regression grade
Description
A 4-tiered tumor regression grading (TRG) system will be used according to the extent of residual carcinoma in the whole tumor area of the esophageal specimen. TRG 1: no residual carcinoma. TRG 2: 1%- 10% residual carcinoma. TRG 3: 11%- 50% residual carcinoma. TRG 4: >50% residual carcinoma
Time Frame
2 years
Title
The total score of participants of both arms will be analyzed and compared.
Description
By World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Taiwan version (2005), quality of life will be assessed at enrollment, at the end of neoadjuvant CRT, and 3 months after surgery. There are 28 subscales in the questionnaire. Each subscale has 5 scores from 1 (the worst) to 5 (the best). The scores of each subscale are summed to be a total score.
Time Frame
2 years
Title
Number of participants with treatment-related adverse events as assessed by the NCI Common Toxicity Criteria (CTC)
Description
By the NCI Common Toxicity Criteria (CTC), version 4.0., number of participants with treatment-related adverse events, all grades and grade 3/4, will be assessed.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically proven squamous cell carcinoma of the intrathoracic esophagus. Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography: A. T3/4a, N0, M0; B. T1-3, N1-3, M0; Tumor length longitudinal ≤ 8cm and radial ≤ 5cm. The tumor must not extend more than 2cm into the stomach. The tumor must not involve cervical esophagus. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. Age ≥ 20 and ≤ 75 years old. Performance status ECOG 0~2. Adequate bone marrow reserves, defined as: A. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; B. platelets ≥ 100,000/µl. Adequate liver function reserves, defined as: A. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); B. serum total bilirubin ≤ 2.0 x upper limit of normal (ULN). Adequate renal function: Creatinine ≤1.5 x upper normal limit or estimated creatinine clearance ≥ 50 ml/min (estimated by Cockcroft-Gault formulation) Written informed consent. Patients must be able to fill in quality of life questionnaires. Exclusion Criteria: Adenocarcinoma. Previous thoracic irradiation. Previous systemic chemotherapy Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer. Prior malignancy, except for the following: A. adequately treated basal cell or squamous cell skin cancer; B. in-situ cervical cancer; C. a "cured" malignancy more than 5 years prior to enrollment. Significant co-morbid disease, which prohibits the conduction of chemotherapy, concurrent chemo- radiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders. Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication. Patients with a history of 2nd or 3rd degree heart block. Pre-existing motor or sensory neurotoxicity greater than grade 1. Patients with prior allergic reactions to drug containing Cremophor, such as teniposide or cyclosporine. Weight loss > 15%. Dementia or altered mental status that would prohibit the understanding and completion of informed consent and questionnaires. Estimated life expectancy less than 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ta-Chen Huang, MD
Phone
+886937817390
Email
e360215@gmail.com
Facility Information:
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ta-Chen Huang, MD
Phone
+886-2-2312-3456
Email
e360215@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Comparing Paclitaxel/Cisplatin and Cisplatin/5-fluorouracil in Neo-CRT for ESCC

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