Epigenetic Priming Using Azacitidine With Neoadjuvant Chemotherapy for Resectable Esophageal Cancer

Phase 1

Completed

• Conditions: Esophageal Cancer; Malignant Neoplasm of Cardio-esophageal Junction of Stomach
• Interventions: Drug: Azacitidine; Drug: Oxaliplatin; Drug: Epirubicin; Drug: Capecitabine

• Registration Number: NCT01386346
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

The purpose of this study is to see whether giving azacitidine before each cycle of chemotherapy prior to surgery is safe.

Detailed Description

Currently patients with resectable (can be removed by surgery) esophageal cancer will receive chemotherapy before surgery to try to shrink the tumor before it is removed. This study will evaluate whether giving azacitidine before each cycle of chemotherapy to increase the shrinkage of the tumor prior to surgery is safe.

Azacitidine is currently approved by the Food and Drug Administration (FDA) for treatment of myelodysplastic syndrome (MDS). Azacitidine is not approved by the FDA for use in this study and is therefore considered investigational. Because azacitidine has not been given before in combination with epirubicin, oxaliplatin and capecitabine, we will also evaluate the safety and tolerability of azacitidine and find out what dose of azacitidine is safe to give with this chemotherapy.

Study Timeline

• Study First Submitted: 2011-05-10
• Study Start: 2011-06
• Study First Submitted QC: 2011-06-29
• Study First Posted: 2011-07-01
• Primary Completion: 2014-08
• Study Completion: 2018-09
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-10
• Last Update Posted: 2018-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Histologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus or gastroesophageal junction (GEJ) and deemed resectable by the thoracic surgeon.
• No prior chemotherapy for esophageal or GEJ cancer.
• ECOG Performance status 0-2.
• Adequate bone marrow, kidney and liver function.
• Ability to understand and the willingness to sign a written informed consent document.
• Subjects of child-bearing potential must agree to use effective means of contraception (men and women).
• Prior malignancy is acceptable if the subject is considered to be cured. In most cases this will mean a 5-year disease-free period.

Exclusion Criteria

• Patients with cervical esophageal cancer or esophageal cancer with squamous cell carcinoma morphology.
• Subjects receiving any other investigational agent or received prior chemotherapy for esophageal or GEJ cancer.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, epirubicin, oxaliplatin, capecitabine and mannitol.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
• Pregnant (positive pregnancy test) or lactating women.
• Patients with active infection, serious inter-current medical conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All subjects	Azacitidine	Azacitidine Dose level -1: 50 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 1: 75 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 2: 75 mg/m2 subcutaneous injection on Day 1-5 of a 21 day cycle. Repeat for a total of 3 cycles. Oxaliplatin on Day 1 130mg/m2 Epirubicin on Day 1 50mg/m2 Capecitabine 625 mg/m2
All subjects	Epirubicin	Azacitidine Dose level -1: 50 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 1: 75 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 2: 75 mg/m2 subcutaneous injection on Day 1-5 of a 21 day cycle. Repeat for a total of 3 cycles. Oxaliplatin on Day 1 130mg/m2 Epirubicin on Day 1 50mg/m2 Capecitabine 625 mg/m2
All subjects	Oxaliplatin	Azacitidine Dose level -1: 50 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 1: 75 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 2: 75 mg/m2 subcutaneous injection on Day 1-5 of a 21 day cycle. Repeat for a total of 3 cycles. Oxaliplatin on Day 1 130mg/m2 Epirubicin on Day 1 50mg/m2 Capecitabine 625 mg/m2
All subjects	Capecitabine	Azacitidine Dose level -1: 50 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 1: 75 mg/m2 subcutaneous injection on Day 1-3 of a 21 day cycle. Repeat for a total of 3 cycles. Dose level 2: 75 mg/m2 subcutaneous injection on Day 1-5 of a 21 day cycle. Repeat for a total of 3 cycles. Oxaliplatin on Day 1 130mg/m2 Epirubicin on Day 1 50mg/m2 Capecitabine 625 mg/m2

Primary Outcome Measures

Name	Time	Method
Evaluation of dose limiting toxicity (DLT)	First 63 days

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States