Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Intervention: cetuximab; cisplatin; paclitaxel; radiation therapy
Intervention description: Weekly with external beam radiation therapy for a total of six doses. The initial dose of cetuximab is 400 mg/m^2 intravenously administered over 120 minutes on day 1, followed by weekly infusions of 250 mg/m^2 intravenously over 60 minutes on days 8, 15, 22, 29, and 36. The infusion rate of cetuximab must never exceed 5 mL/min.; Weekly with external beam radiation therapy for a total of six doses. Patients receive 25 mg/m^2 as an intravenous infusion over 30-60 minutes on days 1, 8, 15, 22, 29 and 36.; Weekly with external beam radiation therapy for a total of six doses. Patients receive 50 mg/m^2 as an intravenous infusion over 1 hour on days 1, 8, 15, 22, 29 and 36.; 1.8 Gy daily for 28 days (over 5-6 weeks) for a total dose of 50.4 Gy.
Intervention MeSH terms: Paclitaxel; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 344.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: stage IIA esophageal cancer; stage IIB esophageal cancer; stage IIIA esophageal cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer; stage IV esophageal cancer; squamous cell carcinoma of the esophagus

Summary:

      RATIONALE: Drugs used in chemotherapy, such as paclitaxel 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. Monoclonal
      antibodies, such as cetuximab, can block tumor growth in different ways. Some block the
      ability of tumor cells to grow and spread. Others find tumor cells and help kill them or
      carry tumor-killing substances to them. Cetuximab may stop the growth of esophageal cancer by
      blocking blood flow to the tumor. It is not yet known whether giving paclitaxel and cisplatin
      together with radiation therapy is more effective with or without cetuximab in treating
      esophageal cancer.

      PURPOSE: This randomized phase III trial is comparing how well giving paclitaxel and
      cisplatin together with radiation therapy works with or without cetuximab in treating
      patients with locally advanced esophageal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically (histologic or cytologic) proven diagnosis of primary squamous cell or
             adenocarcinoma of the esophagus or gastroesophageal junction within 12 weeks prior to
             registration. Patients with involvement of the gastroesophageal junction with Siewert
             type I or II tumors (tumors arising from the distal esophagus and involving the
             esophagogastric junction or tumors starting at the esophagogastric junction and
             involving the cardia) are eligible.

               -  1.1 Disease must be encompassed in a radiotherapy field.

               -  1.2 Patients with celiac, perigastric, mediastinal or supraclavicular adenopathy
                  are eligible.

               -  1.3 Patients with cervical esophageal carcinoma are eligible.

          2. Stage T1N1M0; T2-4, Any N, M0; Any T, Any N, M1a, based upon the following minimum
             diagnostic work-up:

               -  2.1 History/physical examination within 6 weeks prior to registration

               -  2.2 Positron emission tomography (PET)/positron emission tomography-computed
                  tomography (PET-CT) scan (strongly recommended) or chest/abdominal CT within 6
                  weeks prior to registration

               -  2.3 Electrocardiogram (EKG) within 6 weeks of study entry

               -  2.4 Endoscopy with biopsy or cytology by fine needle aspiration (FNA) (must be
                  able to document histologic subtype) within 12 weeks of study entry. Patients
                  with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo
                  bronchoscopy to exclude fistula. (NOTE: Any images from endoscopic procedures up
                  to the time of progression must be kept in the patient's confidential study
                  file.)

          3. Zubrod performance status 0-2

          4. Age ≥ 18 and ≤ 74 (upper limit was set at 74 in an amendment)

          5. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration
             on study, with adequate bone marrow function defined as follows:

               -  5.1 Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

               -  5.2 Platelets ≥ 100,000 cells/mm3

               -  5.3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥8.0 g/dl is acceptable.)

          6. Additional laboratory studies obtained within 2 weeks prior to registration on study

               -  6.1 Creatinine ≤ 1.5 mg/dl

               -  6.2 Bilirubin ≤ 1.5 x upper limit of normal

               -  6.3 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x
                  upper limit of normal

               -  6.4 Serum pregnancy test for women of childbearing potential

          7. Patient's total intake (oral/enteral) must be ≥ 1500 kCal/day

          8. Patient must provide study-specific informed consent prior to study entry

          9. Women of childbearing potential and male participants must practice adequate
             contraception

        Exclusion Criteria:

          1. Evidence of tracheoesophageal fistula, or invasion into the trachea or major bronchi.
             Patients with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo
             bronchoscopy to exclude fistula.

          2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 2 years (For example, carcinoma in situ of the breast, oral cavity,
             or cervix are all permissible).

          3. Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a
             different cancer is allowable.

          4. Prior radiation therapy that would result in overlap of planned radiation therapy
             fields.

          5. Prior therapy that specifically and directly targets the epidermal growth factor
             receptor (EGFR) pathway.

          6. Prior platinum-based and/or paclitaxel-based therapy.

          7. Prior allergic reaction to the study drugs involved in this protocol.

          8. Prior severe infusion reaction to a monoclonal antibody.

          9. Severe, active comorbidity, defined as follows:

               -  9.1 Unstable angina and/or congestive heart failure requiring hospitalization
                  within the last 3 months

               -  9.2 Transmural myocardial infarction within the last 6 months

               -  9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration

               -  9.4 Chronic obstructive pulmonary disease exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy at the time of
                  registration

               -  9.5 Acquired immune deficiency syndrome (AIDS) based upon current Centers for
                  Disease Control and Prevention (CDC) definition; note, however, that human
                  immunodeficiency virus (HIV) testing is not required for entry into this
                  protocol. The need to exclude patients with AIDS from this protocol is necessary
                  because the treatments involved in this protocol may be significantly
                  immunosuppressive. Protocol-specific requirements may also exclude
                  immunocompromised patients.

         10. Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic.

         11. Women who are nursing.