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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

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:

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.

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

NCT ID

NCT03623737

First Posted

June 27, 2017

Last Updated

June 5, 2022

Sponsor

National Taiwan University Hospital

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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

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

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

Time Frame

2 years

Title

The total score of participants of both arms will be analyzed and compared.

Description

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

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

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

e360215@gmail.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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