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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00601705
First received: January 23, 2008
Last updated: November 20, 2014
Last verified: November 2014

January 23, 2008
November 20, 2014
January 2008
June 2012   (final data collection date for primary outcome measure)
Feasibility of resectability rate [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]

Prior experience at this institution suggests a resectability rate after induction chemoradiotherapy of 85-90%, primarily based on disease extent at the time of surgery. Resectability below 75% will suggest that this induction regimen is not feasible.

Similarly, prior experience suggests that post-operative chemoradiotherapy can be given to between 70-80% of resected patients. If adjuvant chemoradiotherapy cannot be given to at least 65% of the resected patients on this trial, the feasibility of this schedule will be in doubt.

  • Feasibility [ Designated as safety issue: No ]
  • Resectability [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00601705 on ClinicalTrials.gov Archive Site
  • Response rate [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]
    Experience with the EOF regimen in patients with advanced disease suggests a response rate of 40%. This is a difficult endpoint in patients with only loco-regional disease. A pathological response rate (pathologic downstaging compared to initial clinical stage) of less than 30% will suggest that this regimen is insufficiently active.
  • Overall survival [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
    A 3-year survival of less than 35% will suggest inefficacy of this treatment protocol. A survival rate greater than 50% would suggest efficacy and justify further study.
  • Locoregional control and distant metastatic control [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]
    A distant metastatic control rate of greater than 55 % would suggest efficacy for this treatment protocol. A locoregional control rate of less than 75% would suggest inefficacy.
  • Toxicity [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  • Response rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Locoregional control and distant metastatic control [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach
A Phase II Trial of Induction Chemotherapy With Epirubicin, Oxaliplatin and Fluorouracil (EOF) Followed by Esophagogastrectomy and Post-operative Concurrent Chemoradiotherapy With Fluorouracil and Cisplatin, in Patients With Loco-regionally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction and Gastric Cardia

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.

OBJECTIVES:

Primary

  • To assess the feasibility and tolerability of induction chemotherapy comprising epirubicin hydrochloride, oxaliplatin, and fluorouracil (EOF), followed by surgical resection and postoperative concurrent chemoradiotherapy comprising fluorouracil and cisplatin in patients with locoregionally advanced adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia.

Secondary

  • To determine the rate of complete and partial response to three courses of EOF induction chemotherapy.
  • To compare the recurrence-free and overall survival of patients treated with this regimen vs historical controls at this institution.
  • To compare patterns of failure in patients treated with this regimen vs historical controls at this institution.

OUTLINE:

  • Induction chemotherapy: Patients receive epirubicin hydrochloride IV over 3-15 minutes and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
  • Surgery: Four weeks after completion of induction chemotherapy, patients with locoregionally confined disease (T0-4, N0-1, M0-1a) undergo transthoracic esophagogastrectomy or total gastrectomy with Roux-en-Y esophagojejunostomy, depending on the location and extent of the tumor at the time of surgery.
  • Postoperative chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo radiotherapy 5 days a week for approximately 6 weeks. Patients also receive fluorouracil IV continuously and cisplatin IV continuously over 96 hours in weeks 1 and 4 of radiotherapy.

After completion of study treatment, patients are followed every 8-12 weeks for 3 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Esophageal Cancer
  • Gastric Cancer
  • Drug: cisplatin
    20 mg/m2/day IV continuous infusion over 24 hours for 96 total hours.
  • Drug: epirubicin hydrochloride
    50 mg/m2 IV bolus
  • Drug: fluorouracil
    200 mg/m2/day will be given as a continuous intravenous infusion for all 9 weeks, beginning on day 1.
  • Drug: oxaliplatin
    130 mg/m2 IV infusion over 2 hours
  • Procedure: adjuvant therapy
    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
  • Procedure: neoadjuvant therapy

    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.

Experimental: Epirubicin, Oxaliplatin and Fluorouracil
Interventions:
  • Drug: cisplatin
  • Drug: epirubicin hydrochloride
  • Drug: fluorouracil
  • Drug: oxaliplatin
  • Procedure: adjuvant therapy
  • Procedure: neoadjuvant therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
61
Not Provided
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00601705
CASE2Y07, P30CA043703, CASE2Y07, NCI-2010-01196
Yes
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: David J. Adelstein, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP