Docetaxel, Oxaliplatin, Capecitabine, Fluorouracil, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Gastric Cancer; Esophageal Cancer; Adenocarcinoma of the Gastroesophageal Junction

Treatments: Drug: capecitabine; Procedure: therapeutic conventional surgery; Drug: fluorouracil; Radiation: radiation therapy; Drug: oxaliplatin; Drug: docetaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00938470

NCI-2011-01930 (Registry Identifier)

NCCTG-N0849

CDR0000646724 (Registry Identifier)

Details and patient eligibility

About

This randomized phase II trial studies how well docetaxel, oxaliplatin, capecitabine, fluorouracil, and radiation therapy works compared with fluorouracil when given together with oxaliplatin and radiation therapy in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as docetaxel, oxaliplatin, capecitabine, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Full description

PRIMARY OBJECTIVES:

I. To assess and compare the pathologic complete response (PCR) rate of patients in Arm A receiving the sequence docetaxel, oxaliplatin, and capecitabine (DOC) followed by 5-fluorouracil (5-FU), oxaliplatin, and radiation therapy (RT) with patients in Arm B receiving only 5-FU, oxaliplatin and RT in patients with potentially resectable adenocarcinoma (ACA) of the esophagus, gastroesophageal junction (GEJ), or gastric cardia.

SECONDARY OBJECTIVES:

I. To assess the adverse event (AE) profile and safety of the proposed treatment in this population.

II. To assess and compare the overall survival (OS) between treatment arms. III. To assess and compare the disease-free survival between treatment arms. IV. To assess and compare the clinical tumor response rate of the proposed regiments when administered before surgery between treatment arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel intravenously (IV) over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil* IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy** 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.

ARM II: Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in Arm I.

• NOTE: * Fluorouracil continuous IV infusion begins within 24 hours of radiotherapy and ends within 24 hours of radiotherapy completion.
• NOTE: ** Radiotherapy should begin within 2-6 weeks after completion of 2 courses of docetaxel, oxaliplatin, and capecitabine.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Enrollment: 73 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Histological confirmation of adenocarcinoma of the esophagus, gastroesophageal (GE) junction, or gastric cardia
• Tumor must be considered surgically resectable; Note: patients with T4N0M0 tumors that are potentially resectable are also eligible
• Nodal involvement: patients with involvement of celiac nodes, (stations 15-20) are eligible if the primary lesion is mid-thoracic, distal esophagus or GE junction; patients with supraclavicular node involvement are eligible with upper thoracic esophagus primary lesions
• Capable of swallowing pills
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Absolute neutrophil count (ANC) >= 1500
• Peripheral platelet count >= 100,000
• Hemoglobin >= 9.0 g/dL
• Total bilirubin =< 1.5 x upper normal limit (UNL)
• Serum glutamic oxaloacetic transaminase (SGOT) (alanine aminotransferase [AST]) =< 3 x UNL
• Creatinine =< 1.5 x UNL
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willingness to return to NCCTG enrolling institution for follow-up
• Patient willing to provide mandatory tissue and blood samples for research purposes
• Patient willing to allow use of FDG PET/CT scans for mandatory research purposes

Exclusion Criteria

• Evidence of distant metastases

• Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic or GE junction

• T1N0M0 or T2N0M0 tumor stage

• Any of the following

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Uncontrolled diabetes (i.e., will interfere with the performance of the FDG PET/CT scans)

• Receiving current treatment or prior treatment for this malignancy

• Other active malignancy 5 years prior to registration, except non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for cancer

• Prior radiation to > 30% of the marrow cavity

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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73 participants in 2 patient groups

Arm I (combination chemotherapy, radiation therapy, surgery)

Experimental group

Description:

Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.

Treatment:

Procedure: therapeutic conventional surgery

Drug: capecitabine

Drug: docetaxel

Drug: fluorouracil

Radiation: radiation therapy

Drug: oxaliplatin

Arm II (oxaliplatin, fluorouracil, radiation, and surgery)

Active Comparator group

Description:

Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in Arm I.

Treatment:

Procedure: therapeutic conventional surgery

Drug: fluorouracil

Radiation: radiation therapy

Drug: oxaliplatin