Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach

NCT00601705 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CASE2Y07P30CA043703NCI-2010-01196
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as epirubicin, oxaliplatin, fluorouracil, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving combination chemotherapy, surgery, and radiation therapy works in treating patients with locoregionally advanced cancer of the esophagus, gastroesophageal junction, or stomach.

Conditions

Esophageal Cancer; Gastric Cancer

Keywords

adenocarcinoma of the esophagus; adenocarcinoma of the stomach; stage III esophageal cancer; stage IV esophageal cancer; stage III gastric cancer; stage IV gastric cancer; stage II esophageal cancer; stage II gastric cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility of Induction Chemoradiotherapy as Measured by Resectability Rate

  Feasibility of induction chemoradiotherapy as measured by resectability in greater than 75% of participants. The number of participants that were resectable.

  at 12 weeks from on study

Secondary Outcomes (5)

• Clinical Response Rate

  at 12 weeks from on study

• Pathological Response Rate

  after completion of study at 35 weeks

• Overall Survival

  at 3 years from on study

• Locoregional Control and Distant Metastatic Control

  at 3 years from on study

• Postoperative Adjuvant Chemoradiotherapy Feasibility

  Between 6 to 10 weeks postoperatively

Study Arms (1)

Epirubicin, Oxaliplatin and Fluorouracil

EXPERIMENTAL

Drug: cisplatin; Drug: epirubicin hydrochloride; Drug: fluorouracil; Drug: oxaliplatin; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

Interventions

cisplatin DRUG

20 mg/m2/day IV continuous infusion over 24 hours for 96 total hours.

Epirubicin, Oxaliplatin and Fluorouracil

epirubicin hydrochloride DRUG

50 mg/m2 IV bolus

Epirubicin, Oxaliplatin and Fluorouracil

fluorouracil DRUG

200 mg/m2/day will be given as a continuous intravenous infusion for all 9 weeks, beginning on day 1.

Epirubicin, Oxaliplatin and Fluorouracil

oxaliplatin DRUG

130 mg/m2 IV infusion over 2 hours

Epirubicin, Oxaliplatin and Fluorouracil

adjuvant therapy PROCEDURE

Between 6-10 weeks after surgery patients will begin postoperative chemoradiotherapy. Daily radiation therapy fractions of 180-200 cGy will be given to the esophago-gastric bed and draining lymphatic regions to a total dose of 50-55 Gy (60 Gy in the event of an R1 or R2 resection). Concurrent with this radiation, two cycles of chemotherapy will be given, during the first and fourth weeks of the radiation

Epirubicin, Oxaliplatin and Fluorouracil

neoadjuvant therapy PROCEDURE

Three weeks after discontinuing the fluorouracil (12 weeks after study entry) patients will be fully restaged to assess for a clinical response, and to ensure that there is no contraindication to surgical resection, which will be scheduled for approximately one week later (13 weeks after study entry). Surgery will consist of a transthoracic esophagogastrectomy or a total gastrectomy with Roux-en-Y esophagojejunostomy depending on the location and extent of the tumor at surgery. An appropriate lymphadenectomy will be performed. Immediate reconstruction is anticipated if possible.

Epirubicin, Oxaliplatin and Fluorouracil

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction or gastric cardia, based on biopsy material or adequate cytologic exam.
• Patients must be clinically staged according to the AJCC 2002 staging system and must have either T3-4, or N1 or M1a disease. Staging should include at least an upper endoscopy with endoscopic ultrasound and an FDG-PET/CT scan.
• Patients must have an ECOG performance status of 0-1.
• Patients must have adequate bone marrow function as evidenced by: Absolute neutrophil count \> 1,500/uL Platelet count \> 100,000/uL
• Patients must have adequate renal function as evidenced by serum creatinine \< 1.6 mg/dL
• Patients must have adequate hepatic function as evidenced by:Serum total bilirubin \< 1.5 mg/dL Alkaline phosphatase \< 3X the institutional ULN AST/ALT \< 3X the institutional ULN
• Patients must have adequate pulmonary function as evidenced by an FEV1 \> 50% predicted.
• Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial.
• Patients of childbearing potential agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method)
• Age \> 18 years

You may not qualify if:

• Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma etc,) will be ineligible.
• Patients with any evidence of distant hematogenous or distant nodal disease (M1b) will be ineligible.
• No prior chemotherapy, radiation therapy or surgery for this malignancy will be allowed. Prior endoscopic debulking, laser therapy or dilatation will not exclude a patient.
• Patients with another active malignancy will not be eligible except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of \< 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of entry
• Patients with an active infection will not be eligible.
• Patients with known hypersensitivity to any of the components of oxaliplatin, epirubicin, fluorouracil or cisplatin will not be eligible.
• Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible.
• Patients with a baseline peripheral neuropathy greater than or equal Grade 2 will not be eligible.
• Patients who are pregnant or lactating will not be eligible.
• Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible.
• Patients with any history of an allogeneic transplant will not be eligible.
• Patients with known infection with HIV, Hepatitis B or C (active, previously treated or both) will not be eligible.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Adenocarcinoma Of Esophagus

Interventions

Cisplatin; Epirubicin; Fluorouracil; Oxaliplatin; Chemotherapy, Adjuvant; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Combined Modality Therapy; Therapeutics; Drug Therapy

Results Point of Contact

• Title: Dr. David Adelstein
• Organization: Cleveland Clinic

ADELSTD@ccf.org

216 444-9310

Study Officials

• David J. Adelstein, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: January 28, 2008
• Study Start: January 5, 2008
• Primary Completion: March 26, 2012
• Study Completion: January 23, 2015
• Last Updated: April 30, 2019
• Results First Posted: April 19, 2019

Record last verified: 2019-04

Locations

US (1)