Preoperative Chemotherapy vs. Chemoradiation in Esophageal / GEJ Adenocarcinoma (POWERRANGER)
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| ClinicalTrials.gov Identifier: NCT01404156 |
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Recruitment Status :
Recruiting
First Posted : July 27, 2011
Last Update Posted : April 1, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
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| Esophageal Cancer Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction | Drug: (Epirubicin Cisplatin 5-Fluorouracil / Xeloda) OR 5-Fluorouracil Leucovorin Oxaliplatin Docetaxel Other: Carboplatin paclitaxel plus concurrent radiotherapy | Phase 2 Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | PreOperative Treatment With chEmotheRapy or chemoRAdiatioN in esophaGeal or gastroEsophageal adenocaRcinoma |
| Actual Study Start Date : | September 2015 |
| Estimated Primary Completion Date : | June 2021 |
| Estimated Study Completion Date : | June 2022 |
| Arm | Intervention/treatment |
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Active Comparator: Neoadjuvant Chemotherapy
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 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 Name: ECF/ECX or FLOT |
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Experimental: Neoadjuvant Chemoradiation
1) -carboplatin and paclitaxel given on days 1, 8, 15, 22 and 29
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Other: Carboplatin paclitaxel plus concurrent radiotherapy
5 cycles carboplatin and paclitaxel given on days 1, 8, 15, 22 and 29 preoperatively:
Radiation Therapy Concurrent radiation therapy will begin within 24 hours of initiation of chemotherapy for patients randomized to chemoradiation treatment. 1. Dose specifications:
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- compliance with assigned neoadjuvant treatment [ Time Frame: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm ]- >60% patients allocated for randomization will start and complete treatment without major protocol violation
- treatment response [ Time Frame: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm ]>30% of patients in both treatment arms demonstrate partial or complete response as defined by Mandard TRG 1-3 on pathologic staging
- survival [ Time Frame: 3 years ]3 year overall- and disease-free survival
- EORTC QOL [ Time Frame: baseline, 3, 6, 9, 12 months post treatment ]European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 Version 3.0
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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): NCT01404156
| Contact: Gordon Buduhan, MD MSc FRCSC | 204-787-3109 | gbuduhan@exchange.hsc.mb.ca | |
| Contact: Kathi Klapp | 204-787-2159 | kathi.klapp@cancercare.mb.ca |
| Canada, Manitoba | |
| Health Sciences Centre / CancerCare Manitoba | Recruiting |
| Winnipeg, Manitoba, Canada, R3A 1R9 | |
| Canada, Ontario | |
| London Health Sciences Centre | Recruiting |
| London, Ontario, Canada, N6A 5W9 | |
| Contact: Deb Lewis 519-685-8500 ext 75685 deb.lewis@lhsc.on.ca | |
| Principal Investigator: Richard Malthaner, MD | |
| Toronto General Hospital / Princess Margaret Hospital | Recruiting |
| Toronto, Ontario, Canada | |
| Contact: Jennifer Lister Jennifer.Lister@uhn.ca | |
| Principal Investigator: Gail Darling, MD | |
| Principal Investigator: | Gordon Buduhan, MD MSc FRCSC | University of Manitoba / CancerCare Manitoba |
| Responsible Party: | Dr. Gordon Buduhan, MD MSc FRCSC Assistant Professor of Surgery Section of Thoracic Surgery,, CancerCare Manitoba |
| ClinicalTrials.gov Identifier: | NCT01404156 |
| Other Study ID Numbers: |
CDHA 174431-7 |
| First Posted: | July 27, 2011 Key Record Dates |
| Last Update Posted: | April 1, 2021 |
| Last Verified: | March 2021 |
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Esophageal cancer Neoadjuvant Chemotherapy Chemoradiation |
Surgery Esophagectomy Adenocarcinoma Gastroesophageal |
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Adenocarcinoma Esophageal Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Head and Neck Neoplasms Digestive System Diseases Esophageal Diseases Gastrointestinal Diseases Leucovorin Paclitaxel |
Docetaxel Cisplatin Carboplatin Fluorouracil Oxaliplatin Epirubicin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites Antimetabolites, Antineoplastic Immunosuppressive Agents |