Clinical trial NCT03991104: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Keywords: esophageal cancer
chemoradiotherapy
oxaliplatin
S-1
Lead sponsor: Zhejiang Provincial People's Hospital
Sponsor class: OTHER
First posted: 2019-06-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Cytopathological confirmed esophageal cancer with unresectable locally advanced diseases;
2. Age of 18-70;
3. ECOG performance status: 0-1;
4. No treatments prior to enrollment;
5. 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.
6. 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.
7. Normal electrocardiogram results and no history of congestive heart failure;
8. Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events;
9. Informed consent signed.

Exclusion Criteria:

1. Prior treatments of chemotherapy or irradiation;
2. Poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable;
3. Contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis;
4. Participating in other clinical trials;
5. Pregnancy, breast feeding, or not adopting birth control;
6. 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;
7. Weight loss of 20% or more of normal body weight within 3 months.
8. 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;

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 1 month
measure: Response rate
timeFrame: 1 month
Secondary outcomes:
measure: Recommended dose of Oxaliplatin for phase II trial.
timeFrame: 1 month
measure: Number of Participants with Adverse Events (Phase II).
timeFrame: 6 months
measure: Overall survival time
timeFrame: 0-2 years
measure: Progression-free survival time
timeFrame: 0-2 years
Other outcomes:
measure: Health-related Quality of life (HR-QoL, Phase II)
timeFrame: 0-2 years
measure: Health-related Quality of life (HR-QoL, Phase II)
timeFrame: 0-2 years
Locations:
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
References: