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Feasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer (SOX)

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ClinicalTrials.gov Identifier: NCT02347904
Recruitment Status : Recruiting
First Posted : January 28, 2015
Last Update Posted : June 27, 2018
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.


Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: S-1 and Oxaliplatin Phase 1

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

  1. Percentage of patients completing 6 cycles of S-1 (with or without oxaliplatin).
  2. Dose modifications (ie, delays, dose reductions, or interruptions) for S-1.
  3. Dose modifications (ie, delays, dose reductions, or interruptions) for oxaliplatin.
  4. Dose intensity of S-1.
  5. Dose intensity of oxaliplatin.
  6. Toxicity.
  7. Disease free survival.

Exploratory Objectives

  1. Assessment of pharmacokinetics of S1 as predictive factors for efficacy and toxicity.
  2. Potential biomarker development based on assessment of archived tumor tissue and blood samples and the proposed mechanism of action of study drugs.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility Study of Adjuvant Treatment With S-1 and Oxaliplatin in Patients With Resectable Esophageal Cancer
Study Start Date : December 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arm Intervention/treatment
Experimental: Adjuvant S-1 and Oxaliplatin
Adjuvant treatment with s-1 and oxaliplatin after neoadjuvant chemoradiation and esophagectomy in patients with resectable esophageal cancer
Drug: S-1 and Oxaliplatin
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
Other Name: Teysuno




Primary Outcome Measures :
  1. The percentage of patients completing the preplanned number of 6 cycles of SOX. [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Percentage of patients completing 6 cycles of S-1 (with or without oxaliplatin) [ Time Frame: 24 months ]
  2. Dose modifications for S-1 [ Time Frame: 24 months ]
    in terms of delay of treatment in weeks

  3. Dose modifications for S-1 [ Time Frame: 24 months ]
    in terms of dose reduction in percentage of orginal dose

  4. Dose modifications for S-1 [ Time Frame: 24 months ]
    in terms of number of interruptions of treatment

  5. Dose modifications for Oxaliplatin [ Time Frame: 24 months ]
    in terms of delay of treatment in weeks

  6. Dose modifications for Oxaliplatin [ Time Frame: 24 months ]
    in terms of dose reduction in percentage of orginal dose

  7. Dose modifications for Oxaliplatin [ Time Frame: 24 months ]
    in terms of number of interruptions of treatment

  8. Dose intensity for S-1 [ Time Frame: 24 months ]
    total received dose of S-1 in mg/m2 per week

  9. Dose intensity for Oxaliplatin [ Time Frame: 24 months ]
    total received dose of oxaliplatin in mg/m2 per week

  10. Toxicity [ Time Frame: 24 months ]
    in terms of CTCAE v4.0 criteria

  11. Disease free survival [ Time Frame: 24 months ]
    in months

  12. Overall survival [ Time Frame: 24 months ]
    in months


Other Outcome Measures:
  1. AUC of S-1 [ Time Frame: 24 months ]
    assessment of pharmacokinetics (Cmax/T1/2) in relation to toxicity in terms of CTCAE criteria and efficacy in terms of disease free survival



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02347904


Contacts
Contact: H WM van Laarhoven, MD,PHD,PHD 31 20 5665955 ext 65955 h.vanlaarhoven@amc.nl
Contact: E H van Daalen 31 20 5668229 ext 68229 trialmedonc@amc.nl

Locations
Netherlands
Academic Medical Center, Medical Oncology Recruiting
Amsterdam, Netherlands, 1100 DD
Contact: H WM van Laarhoven, MD, PhD, PhD    31 20 5665955    h.vanlaarhoven@amc.uva.nl   
Contact: E. H. vandaalen    31 20 5668229    trialmedonc@amc.uva.nl   
Principal Investigator: H. WM van Laarhoven, MD, PhD, PhD         
Sub-Investigator: S O. van der Woude, MD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Celgene Corporation
Investigators
Principal Investigator: H WM van Laarhoven, MD,PHD,PHD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Responsible Party: H.W.M. van Laarhoven, Prof. Dr. H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02347904     History of Changes
Other Study ID Numbers: NL49889.018.14
First Posted: January 28, 2015    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

Keywords provided by H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Esophageal cancer
Adjuvant treatment
S-1
Oxaliplatin
Feasibility

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Oxaliplatin
Antineoplastic Agents