Preoperative Chemotherapy vs. Chemoradiation in Esophageal / GEJ Adenocarcinoma

NCT01404156 | Completed Phase 2 DMC

• 1 other identifier: CDHA 174431-7
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief 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

Keywords

Esophageal cancer; Neoadjuvant; Chemotherapy; Chemoradiation; Surgery; Esophagectomy; Adenocarcinoma; Gastroesophageal

Outcome Measures

Primary Outcomes (2)

• compliance with assigned neoadjuvant treatment

  \- \>60% patients allocated for randomization will start and complete treatment without major protocol violation

  5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm

• treatment response

  \>30% of patients in both treatment arms demonstrate partial or complete response as defined by Mandard TRG 1-3 on pathologic staging

  5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm

Secondary Outcomes (2)

• survival

  3 years

• EORTC QOL

  baseline, 3, 6, 9, 12 months post treatment

Study Arms (2)

Neoadjuvant Chemotherapy

ACTIVE COMPARATOR

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 intravenous infusionIV infusion 5-FU may be substituted with Capecitabine (Xeloda) 625mg/m2 PO BID (ECX)

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

Neoadjuvant Chemoradiation

EXPERIMENTAL

1\) -carboplatin and paclitaxel given on days 1, 8, 15, 22 and 29 * 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. 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.

Other: Carboplatin paclitaxel plus concurrent radiotherapy

Interventions

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

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)

Also known as: ECF/ECX or FLOT

Neoadjuvant Chemotherapy

Carboplatin paclitaxel plus concurrent radiotherapy OTHER

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 .

Neoadjuvant Chemoradiation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adenocarcinoma of esophagus or gastroesophageal junction; -cT1N1-3 or T2-4Nx; M0 by American Joint Committee on Cancer (AJCC) 7th Edition staging classification
• proximal portion of the tumor at least 20 cm from the incisors on endoscopy, and extend no greater than 2 cm into the gastric cardia
• tumor length \< 8cm; diameter \< 5 cm
• age \> 18 years
• absolute neutrophil count (ANC) ≥ 1.5 x 109 / L
• platelet count \> 100 x 109 / L
• creatinine clearance \> 50 ml / min
• bilirubin \< 1.5x upper limit normal
• FEV1 \> 1.0 L
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

You may not qualify if:

• positive serum / urine pregnancy test for females of childbearing age
• previous chemotherapy for esophageal cancer
• previous radiation therapy that would overlap required radiation fields
• major systemic illness(es) that would limit life expectancy \<2 years
• psychiatric / cognitive illness that would limit ability to give informed consent
• (Patients will be reviewed by both a medical and radiation oncologist and deemed fit to undergo either neoadjuvant chemotherapy or chemoradiation, respectively)

Sponsors & Collaborators

• Dr. Gordon Buduhan: lead
• CancerCare Manitoba: collaborator
• University of Toronto: collaborator
• London Health Sciences Centre: collaborator

Study Sites (3)

Health Sciences Centre / CancerCare Manitoba

Winnipeg, Manitoba, R3A 1R9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Toronto General Hospital / Princess Margaret Hospital

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus; Adenocarcinoma

Interventions

Capecitabine; CP protocol

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gordon Buduhan, MD MSc FRCSC

  University of Manitoba / CancerCare Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD MSc FRCSC Associate Professor of Surgery Section of Thoracic Surgery,

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: July 27, 2011
• Study Start: September 1, 2015
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

CA (3)