Back to resultsSOX-based CRT for Esophageal Cancer.
Primary Purpose
Esophageal Cancer
Status
Withdrawn
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Oxaliplatin
S-1 capsule
Intensity modulated radiotherapy (IMRT)
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Cancer focused on measuring esophageal cancer, chemoradiotherapy, oxaliplatin, S-1
Eligibility Criteria
Inclusion Criteria:
- Cytopathological confirmed esophageal cancer with unresectable locally advanced diseases;
- Age of 18-70;
- ECOG performance status: 0-1;
- No treatments prior to enrollment;
- Patients must have measurable or evaluable disease with at least one tumor mass maximum diameter ≥10mm by multi-slice spiral CT or MR scan. Imaging exam must be performed within 15 days from enrollment.
- Normal marrow function and the blood tests must be collected within 7 days from enrollment with a hemoglobin of ≥90g/L, an white blood cell (WBC) counts of ≥4.0×109/L，a neutrophil count of ≥2.0×109/L, , a platelet count of ≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. Pulmonary function (FEV1 >1L), and no major electrocardiogram abnormalities.
- Normal electrocardiogram results and no history of congestive heart failure;
- Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events;
- Informed consent signed.
Exclusion Criteria:
- Prior treatments of chemotherapy or irradiation;
- Poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable;
- Contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis;
- Participating in other clinical trials;
- Pregnancy, breast feeding, or not adopting birth control;
- Clinically significant and uncontrolled major medical conditions including but not limited to: active uncontrolled infection, symptomatic congestive heart failure, Unstable angina pectoris or cardiac arrhythmia, psychiatric illness/ social situation that would limit compliance with study requirements; any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities;
- Weight loss of 20% or more of normal body weight within 3 months.
- The subject has had another active malignancy within the past five years except for cervical cancer in site, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin;
Sites / Locations
- Zhejiang Provincial People's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SOX-based Chemoradiotherapy
Arm Description
IMRT is delivered with a daily fraction of 1.8 Gy to a total dose of 50.4 Gy over 5 weeks. Concurrent Oxaliplatin (3 levels for phase I: 110mg/m², 120 mg/m² and 130 mg/m², d1) and fixed dose of S-1 (80mg/ m², d1-14) are administered concurrently with IMRT, every 4 weeks. The recommended dose of Oxaliplatin are then further evaluated in the Phase II setting.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
Phase I: toxicities will be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0).
Response rate
Phase II: Response rate will be done after 4 weeks following the last radiotherapy session as evaluated by RECIST 1.1.
Secondary Outcome Measures
Recommended dose of Oxaliplatin for phase II trial.
To determine the recommended phase II dose (RD) of Oxaliplatin with fixed dose of S-1 in combination with IMRT for esophageal cancer (Phase I).
Number of Participants with Adverse Events (Phase II).
Both the number of subjects with adverse events and the degree of the adverse events of each participant according to NCI CTCAE version 4.0 will be recorded. And the outcome of each adverse event will be followed.
Overall survival time
Overall survival (OS) is determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.
Progression-free survival time
Progression-free survival (PFS) is calculated from the date of CRT initiation to the date of documented failure (local recurrence or metastasis occurrence) or the date of the last follow-up for those remaining.
Full Information
NCT ID
NCT03991104
First Posted
June 15, 2019
Last Updated
September 17, 2023
Sponsor
Zhejiang Provincial People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03991104
Brief Title
SOX-based CRT for Esophageal Cancer.
Official Title
A Phase I/II Study of S-1 and Oxaliplatin Based Definitive Concurrent Chemoradiotherapy (SOX-CRT-01) for Unresectable Locally Advanced Esophageal Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No eligible patients enrolled. We have to withdraw the trial.
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang Provincial People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Patients with esophageal cancer that had locally advanced diseases or with unresectable diseases are being asked to participate in this phase I/II study.
This phase I/II study is being conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of IMRT combined with S-1 and Oxaliplatin (SOX) based chemotherapy for unresectable locally advanced esophageal cancer.
Detailed Description
Esophageal carcinoma (EC) remains difficult to cure with overall 5-year survival rates for locally advanced stages being poor. Definitive concurrent chemoradiotherapy (dCRT) remains the mainstay of treatment for locally advanced and unresectable EC. Oxaliplatin is a new generation platinum with a more preferable toxicity profile compared to cisplatin. Furthermore, S-1 combines 5-Fu prodrug (tegafur) and two modulators of 5-Fu metabolism, gimeracil (CDHP) and oteracil. Basic studies showed that S-1 has superior anti-cancer effects than 5-Fu and enhances the sensitivity of cancer cells to the effects of radiotherapy. Herein, we designed a prospective phase I/II study, which is combined S-1 and oxaliplatin with IMRT for the patients with locally advanced and unresectable esophageal cancer, and evaluated the tolerability and efficacy of this combination.
<Phase I>
Primary Objective:
To establish the safety of combination chemotherapy comprising oxaliplatin (escalating doses: 110, 120, 130 mg/m2, day 1 and day 29), fixed dose of S-1 (80 mg/m2, day1-14 and day 29-42) and IMRT (5040cGy/28fx/5W+) in unresectable locally advanced esophageal cancer.
Secondary Objective:
To observe the efficacy of this regimen in these patients.
<Phase II>
Primary Objective:
To assess the response rate of combination chemotherapy comprising oxaliplatin (recommended dose determined in phase I study, day1 and day29), fixed dose of S-1 (80 mg/m2, day1-14 and day 29-42), and IMRT (5040cGy/28fx/5W+) in unresectable locally advanced esophageal cancer.
Secondary Objectives:
To determine the adverse reactions of this regimen in these patients. To determine PFS(Progression free survival) of patients treated with this regimen.
To determine OS (overall survival) of patients treated with this regimen. To explore the Health-related Quality of life using EORTC QLQ-C30 and EORTC QLQ-OES18 in these patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
esophageal cancer, chemoradiotherapy, oxaliplatin, S-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SOX-based Chemoradiotherapy
Arm Type
Experimental
Arm Description
IMRT is delivered with a daily fraction of 1.8 Gy to a total dose of 50.4 Gy over 5 weeks. Concurrent Oxaliplatin (3 levels for phase I: 110mg/m², 120 mg/m² and 130 mg/m², d1) and fixed dose of S-1 (80mg/ m², d1-14) are administered concurrently with IMRT, every 4 weeks. The recommended dose of Oxaliplatin are then further evaluated in the Phase II setting.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin (3 levels for phase I: 110 mg/m², 120 mg/m² and 130 mg/m²) is administered as a 2 h intravenous infusion in 500 mL of 5% glucose on day 1 and day 29 during the treatment course.
Intervention Type
Drug
Intervention Name(s)
S-1 capsule
Intervention Description
Patients received a fixed dose of S-1 with a dose of 80 mg/m2/d twice daily for 2 weeks, every 4 weeks.
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated radiotherapy (IMRT)
Intervention Description
The total radiation dose was set to 50.4 Gy, which was given in 28 fractions of 1.8 Gy once-daily fractions for over 5 weeks.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Phase I: toxicities will be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0).
Time Frame
1 month
Title
Response rate
Description
Phase II: Response rate will be done after 4 weeks following the last radiotherapy session as evaluated by RECIST 1.1.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Recommended dose of Oxaliplatin for phase II trial.
Description
To determine the recommended phase II dose (RD) of Oxaliplatin with fixed dose of S-1 in combination with IMRT for esophageal cancer (Phase I).
Time Frame
1 month
Title
Number of Participants with Adverse Events (Phase II).
Description
Both the number of subjects with adverse events and the degree of the adverse events of each participant according to NCI CTCAE version 4.0 will be recorded. And the outcome of each adverse event will be followed.
Time Frame
6 months
Title
Overall survival time
Description
Overall survival (OS) is determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.
Time Frame
0-2 years
Title
Progression-free survival time
Description
Progression-free survival (PFS) is calculated from the date of CRT initiation to the date of documented failure (local recurrence or metastasis occurrence) or the date of the last follow-up for those remaining.
Time Frame
0-2 years
Other Pre-specified Outcome Measures:
Title
Health-related Quality of life (HR-QoL, Phase II)
Description
In phase II trial, HR-QoL would be measured by standardized EORTC questionaires (EORTC QLQ-C30).
Time Frame
0-2 years
Title
Health-related Quality of life (HR-QoL, Phase II)
Description
In phase II trial, HR-QoL would be measured by standardized EORTC questionaires (EORTC QLQ-OES18).
Time Frame
0-2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Cytopathological confirmed esophageal cancer with unresectable locally advanced diseases;
Age of 18-70;
ECOG performance status: 0-1;
No treatments prior to enrollment;
Patients must have measurable or evaluable disease with at least one tumor mass maximum diameter ≥10mm by multi-slice spiral CT or MR scan. Imaging exam must be performed within 15 days from enrollment.
Normal marrow function and the blood tests must be collected within 7 days from enrollment with a hemoglobin of ≥90g/L, an white blood cell (WBC) counts of ≥4.0×109/L，a neutrophil count of ≥2.0×109/L, , a platelet count of ≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. Pulmonary function (FEV1 >1L), and no major electrocardiogram abnormalities.
Normal electrocardiogram results and no history of congestive heart failure;
Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events;
Informed consent signed.
Exclusion Criteria:
Prior treatments of chemotherapy or irradiation;
Poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable;
Contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis;
Participating in other clinical trials;
Pregnancy, breast feeding, or not adopting birth control;
Clinically significant and uncontrolled major medical conditions including but not limited to: active uncontrolled infection, symptomatic congestive heart failure, Unstable angina pectoris or cardiac arrhythmia, psychiatric illness/ social situation that would limit compliance with study requirements; any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities;
Weight loss of 20% or more of normal body weight within 3 months.
The subject has had another active malignancy within the past five years except for cervical cancer in site, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin;
Facility Information:
Facility Name
Zhejiang Provincial People's Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
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SOX-based CRT for Esophageal Cancer.
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