Clinical trial NCT01404156: Preoperative Chemotherapy vs. Chemoradiation in Esophageal / GEJ Adenocarcinoma
Official title: PreOperative Treatment With chEmotheRapy or chemoRAdiatioN in esophaGeal or gastroEsophageal adenocaRcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Esophageal Cancer
Adenocarcinoma, Esophageal
Adenocarcinoma, Gastroesophageal Junction
Keywords: Esophageal cancer
Neoadjuvant
Chemotherapy
Chemoradiation
Surgery
Esophagectomy
Adenocarcinoma
Gastroesophageal
Lead sponsor: CancerCare Manitoba
Sponsor class: OTHER
Collaborators: name: CancerCare Manitoba
name: University of Toronto
name: London Health Sciences Centre
First posted: 2011-07-27
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVE To determine the feasibility of a randomized trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation for patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction.

RESEARCH PLAN Phase III randomized 2-arm parallel group pilot study

1:1 randomization to A) or B)

TREATMENT REGIMEN A) PERIOPERATIVE CHEMOTHERAPY (OPTION of CHEMO REGIMEN 1 or 2) 1) FLOT - Four x 14 day cycles FLOT preoperatively and 4 cycles postoperatively: 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

OR

2) ECF / ECX - Three x 21-day cycles ECF preoperatively and 3 cycles postoperatively (within 4-10 weeks after surgery): Epirubicin (50 mg/m²,) day 1 IV Cisplatin: 60 mg/m², day 1 IV 5-Fluorouracil: 200 mg/m², daily for 21 days by continuous IV infusion 5-FU may be substituted with Capecitabine (Xeloda) 625mg/m2, BID (ECX)

OR

B) NEOADJUVANT CHEMORADIATION

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

* paclitaxel: 50 mg / m2 IV
* carboplatin: dosed to an area under the curve of 2, by Calvert formula Radiation Therapy 45-50.4 Gy in 25-28 fractions of 1.8 Gy/fraction, 5 fractions/wk 45-50.4 Gy in 25-28 fractions of 1.8 Gy/fraction, 5 fractions/wk Upon completion of neoadjuvant therapy, all patients will be considered for surgery.

Patients will be deemed acceptable for surgery provided:

* repeat imaging performed after neoadjuvant therapy does not demonstrate distant metastases or local invasion of the primary tumor into vital structures (heart, great vessels, trachea)
* maintenance of adequate performance status and ability to tolerate esophagectomy

Surgery will be performed preferably within 8 weeks of completion of neoadjuvant therapy.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria

* positive serum / urine pregnancy test for females of childbearing age
* previous primary / recurrent malignancy in last 5 years (history of previous / current non-melanoma skin cancer or cervical in-situ carcinoma in last 5 years acceptable for inclusion in trial)
* 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)

Primary outcomes:
measure: compliance with assigned neoadjuvant treatment
timeFrame: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm
measure: treatment response
timeFrame: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm
Secondary outcomes:
measure: survival
timeFrame: 3 years
measure: EORTC QOL
timeFrame: baseline, 3, 6, 9, 12 months post treatment
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Health Sciences Centre / CancerCare Manitoba
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital / Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University of Manitoba / CancerCare Manitoba
name: Gordon Buduhan, MD MSc FRCSC
role: PRINCIPAL_INVESTIGATOR
References: