Back to resultsFeasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer (SOX)
Primary Purpose
Esophageal Cancer
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
S-1 and Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Cancer focused on measuring Esophageal cancer, Adjuvant treatment, S-1, Oxaliplatin, Feasibility
Eligibility Criteria
Inclusion Criteria:
- Radically resected adenocarcinoma of the esophagus
- Completed neoadjuvant treatment with paclitaxel 50 mg/m2 and carboplatin Area Under Curve (AUC) = 2 on days 1, 8, 15, 22 and 29 and radiotherapy to a total dose of 41.4 Gy in 23 fractions of 1.8 Gy, 5 fractions per week.
- Age ≥ 18 years
- WHO performance status 0-1
- Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥1.0 x 109/L, - platelets ≥ 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, ≥30 ml/min), liver function (serum bilirubin ≤ 2 x Upper Limit Normal (ULN), serum transaminases ≤ 3 x).
- Negative pregnancy test in women with childbearing potential.
- Expected adequacy of follow-up.
- Written informed consent.
Exclusion Criteria:
- Any history or clinical signs of metastasis
- History of a second malignancy <5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.
- Significant cardiovascular disease < 1 yr before start of the study (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism).
- Chronic active infection.
- Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs.
- Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as CTC grade 2 or higher), malabsorption syndrome, bowel obstruction, or inability to swallow tablets).
- Concomitant treatments: concomitant (or within 4 weeks before start of the study) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy.
- Continuous use of systemic immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).
Sites / Locations
- Academic Medical Center, Medical Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Adjuvant S-1 and Oxaliplatin
Arm Description
Adjuvant treatment with s-1 and oxaliplatin after neoadjuvant chemoradiation and esophagectomy in patients with resectable esophageal cancer
Outcomes
Primary Outcome Measures
The percentage of patients completing the preplanned number of 6 cycles of SOX.
Secondary Outcome Measures
Percentage of patients completing 6 cycles of S-1 (with or without oxaliplatin)
Dose modifications for S-1
in terms of delay of treatment in weeks
Dose modifications for S-1
in terms of dose reduction in percentage of orginal dose
Dose modifications for S-1
in terms of number of interruptions of treatment
Dose modifications for Oxaliplatin
in terms of delay of treatment in weeks
Dose modifications for Oxaliplatin
in terms of dose reduction in percentage of orginal dose
Dose modifications for Oxaliplatin
in terms of number of interruptions of treatment
Dose intensity for S-1
total received dose of S-1 in mg/m2 per week
Dose intensity for Oxaliplatin
total received dose of oxaliplatin in mg/m2 per week
Toxicity
in terms of CTCAE v4.0 criteria
Disease free survival
in months
Overall survival
in months
Full Information
NCT ID
NCT02347904
First Posted
December 16, 2014
Last Updated
November 15, 2019
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Celgene Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02347904
Brief Title
Feasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer
Acronym
SOX
Official Title
Feasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
December 2014 (Actual)
Primary Completion Date
November 2019 (Actual)
Study Completion Date
November 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Celgene Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this prospective single arm study the investigators will assess the feasibility of S-1 and Oxaliplatin as adjuvant treatment in patients with esophageal cancer.
The primary objective is to assess the feasibility of administering adjuvant S-1 and Oxaliplatin (SOX) in patients with esophageal cancer after neoadjuvant chemoradiotherapy with paclitaxel and carboplatin and esophagectomy. Primary end point is the percentage of patients completing the preplanned number of 6 cycles of SOX.
Detailed Description
Since the outcome of patients with esophageal cancer treated with neoadjuvant chemoradiation and surgery is still poor, strategies to improve survival should be explored. The benefit of adjuvant chemotherapy after neoadjuvant chemoradiotherapy followed by surgery is unknown. Preferably, such adjuvant chemotherapy regimen should consist of a non-cross resistant, well-tolerated schedule. For this purpose, the combination of S-1, an oral fluoropyrimidine, with oxaliplatin, may be of benefit, as each of these compounds have shown efficacy in gastroesophageal cancer. Also, importantly, the combination of S-1 with oxaliplatin (SOX) in advanced gastric cancer was well-tolerated. Nevertheless, it should be acknowledged that after major surgery for esophageal cancer, adjuvant treatment with combination chemotherapy may be hard to accomplish as was shown in the MAGIC trial for gastric cancer where less than half of all patients completed adjuvant therapy.
Therefore the investigators want to assess the feasibility of an adjuvant treatment scheme with S-1 and Oxaliplatin. When the proposed treatment scheme is feasible the potential benefit on survival will be evaluated in further studies. Feasibility is defined ≥50% of patients completing the pre-planned number of cycles
Study Objectives Primary Objective To assess the feasibility of administering adjuvant SOX in patients with esophageal cancer after neoadjuvant chemoradiotherapy with paclitaxel and carboplatin and esophagectomy
Secondary Objectives
Percentage of patients completing 6 cycles of S-1 (with or without oxaliplatin).
Dose modifications (ie, delays, dose reductions, or interruptions) for S-1.
Dose modifications (ie, delays, dose reductions, or interruptions) for oxaliplatin.
Dose intensity of S-1.
Dose intensity of oxaliplatin.
Toxicity.
Disease free survival.
Exploratory Objectives
Assessment of pharmacokinetics of S1 as predictive factors for efficacy and toxicity.
Potential biomarker development based on assessment of archived tumor tissue and blood samples and the proposed mechanism of action of study drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
Esophageal cancer, Adjuvant treatment, S-1, Oxaliplatin, Feasibility
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adjuvant S-1 and Oxaliplatin
Arm Type
Experimental
Arm Description
Adjuvant treatment with s-1 and oxaliplatin after neoadjuvant chemoradiation and esophagectomy in patients with resectable esophageal cancer
Intervention Type
Drug
Intervention Name(s)
S-1 and Oxaliplatin
Other Intervention Name(s)
Teysuno
Intervention Description
Six courses of oxaliplatin (130 mg/m2) intravenously on day 1 and S-1 (25 mg/m2 b.i.d.) orally from day 1 to 14 every 3 weeks, starting within 12 weeks after esophagectomy
Primary Outcome Measure Information:
Title
The percentage of patients completing the preplanned number of 6 cycles of SOX.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Percentage of patients completing 6 cycles of S-1 (with or without oxaliplatin)
Time Frame
24 months
Title
Dose modifications for S-1
Description
in terms of delay of treatment in weeks
Time Frame
24 months
Title
Dose modifications for S-1
Description
in terms of dose reduction in percentage of orginal dose
Time Frame
24 months
Title
Dose modifications for S-1
Description
in terms of number of interruptions of treatment
Time Frame
24 months
Title
Dose modifications for Oxaliplatin
Description
in terms of delay of treatment in weeks
Time Frame
24 months
Title
Dose modifications for Oxaliplatin
Description
in terms of dose reduction in percentage of orginal dose
Time Frame
24 months
Title
Dose modifications for Oxaliplatin
Description
in terms of number of interruptions of treatment
Time Frame
24 months
Title
Dose intensity for S-1
Description
total received dose of S-1 in mg/m2 per week
Time Frame
24 months
Title
Dose intensity for Oxaliplatin
Description
total received dose of oxaliplatin in mg/m2 per week
Time Frame
24 months
Title
Toxicity
Description
in terms of CTCAE v4.0 criteria
Time Frame
24 months
Title
Disease free survival
Description
in months
Time Frame
24 months
Title
Overall survival
Description
in months
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
AUC of S-1
Description
assessment of pharmacokinetics (Cmax/T1/2) in relation to toxicity in terms of CTCAE criteria and efficacy in terms of disease free survival
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Radically resected adenocarcinoma of the esophagus
Completed neoadjuvant treatment with paclitaxel 50 mg/m2 and carboplatin Area Under Curve (AUC) = 2 on days 1, 8, 15, 22 and 29 and radiotherapy to a total dose of 41.4 Gy in 23 fractions of 1.8 Gy, 5 fractions per week.
Age ≥ 18 years
WHO performance status 0-1
Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥1.0 x 109/L, - platelets ≥ 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, ≥30 ml/min), liver function (serum bilirubin ≤ 2 x Upper Limit Normal (ULN), serum transaminases ≤ 3 x).
Negative pregnancy test in women with childbearing potential.
Expected adequacy of follow-up.
Written informed consent.
Exclusion Criteria:
Any history or clinical signs of metastasis
History of a second malignancy <5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin.
Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.
Significant cardiovascular disease < 1 yr before start of the study (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism).
Chronic active infection.
Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs.
Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as CTC grade 2 or higher), malabsorption syndrome, bowel obstruction, or inability to swallow tablets).
Concomitant treatments: concomitant (or within 4 weeks before start of the study) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy.
Continuous use of systemic immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
H WM van Laarhoven, MD,PHD,PHD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Medical Center, Medical Oncology
City
Amsterdam
ZIP/Postal Code
1100 DD
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Feasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer
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