Preoperative Chemotherapy vs. Chemoradiation in Esophageal / GEJ Adenocarcinoma

Summary

The best treatment for resectable esophageal or gastroesophageal adenocarcinoma is unknown. Although an operation to remove the esophagus is the most common treatment, previous studies have shown that patients live longer when either perioperative (before and after surgery) chemotherapy or preoperative (before surgery) chemotherapy plus radiation is given, compared to surgery alone. However it is unknown which of these treatments (perioperative chemotherapy or preoperative chemoradiation) is more effective in improving survival. A study where patients with resectable esophageal / GE junction cancer are chosen at random to receive one of the two preoperative treatments would help determine if one form of treatment improves survival compared to the other.

Patients with localized esophageal / GE junction cancer (adenocarcinoma) will be randomized to receive either preoperative and postoperative chemotherapy or preoperative chemoradiation followed by surgery.

The main objective of this pilot trial is to determine the possibility of conducting a larger study with many centers participating. If this study proves to be feasible with enough patients enrolled and able to tolerate treatments without major side effects then we can hopefully proceed to perform a larger multi-center trial to look for survival outcome differences between patients who receive preoperative chemotherapy and those who receive preoperative chemoradiation. The results of this trial would ultimately help us choose the most effective treatment of resectable esophageal cancer and hopefully improve survival.

Conditions

• Esophageal Cancer
• Adenocarcinoma, Esophageal
• Adenocarcinoma, Gastroesophageal Junction

Interventions

DRUG

(Epirubicin Cisplatin 5-Fluorouracil / Xeloda) OR 5-Fluorouracil Leucovorin Oxaliplatin Docetaxel

NEOADJUVANT CHEMOTHERAPY (OPTION of CHEMO REGIMEN 1 or 2) 1\) FLOT - Four x 14 day cycles FLOT preoperatively and 4 cycles postoperatively (within 4-10 weeks after surgery): 5-Fluorouracil 2600 mg/m², day 1 IV every 14 days Leucovorin 200 mg/m², day 1, IV., every 14 days Oxaliplatin 85 mg/m², day 1, IV, every 14 days Docetaxel 50mg/m2, day 1, IV, every 14 days 2\) ECF / ECX - Three x 21-day cycles ECF preoperatively and 3 cycles postoperatively (within 4-10 weeks after surgery): Epirubicin (50 mg/m²,mg per square meter of body-surface area) by intravenous bolus on day 1 IV Cisplatin: 60 mg/m², mg per square meter intravenously with hydration on day 1 IV 5-Fluorouracil: 200 mg/m², mg per square meter daily for 21 days by continuous IV infusion 5-FU may be substituted with Capecitabine (Xeloda) 625mg/m2, PO BID (ECX)

OTHER

Carboplatin paclitaxel plus concurrent radiotherapy

5 cycles carboplatin and paclitaxel given on days 1, 8, 15, 22 and 29 preoperatively: * paclitaxel: 50 mg / m2 IV over 1 hour * carboplatin: dosed to an area under the curve of 2, by Calvert formula, as a 1 hour IV infusion Radiation Therapy Concurrent radiation therapy will begin within 24 hours of initiation of chemotherapy for patients randomized to chemoradiation treatment. 1\. Dose specifications: 1. Phase 1: Total radiation prescription dose 45 Gy given in 25 fractions of 1.8 Gy per fraction, 5 fractions / week, one treatment / day, starting on the first day of first cycle of chemotherapy. This total radiation dose option is acceptable if boost dose is not possible due to clinical reasons or dosimetric constraints. 2. Phase 2: (GTV only) Boost is not mandatory and up to the discretion of radiation oncologist. Total radiation prescription dose 5.4 Gy given in 3 fractions of 1.8 Gy per fraction, 5 fractions / week, one treatment .

Sponsors & Collaborators

• CancerCare Manitoba

  collaborator OTHER

• University of Toronto

  collaborator OTHER

• London Health Sciences Centre

  collaborator OTHER

• Dr. Gordon Buduhan

  lead OTHER

Principal Investigators

• Gordon Buduhan, MD MSc FRCSC · University of Manitoba / CancerCare Manitoba

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-09-30

Primary Completion

2023-08-31

Completion

2023-08-31

Countries

• Canada

Study Locations