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Phase 3 N=203 Randomized Treatment

Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

Esophageal Adenocarcinoma · Gastroesophageal Junction Adenocarcinoma · Stage IB Esophageal Cancer AJCC v7 · Stage IIA Esophageal Cancer AJCC v7 · Stage IIB Esophageal Cancer AJCC v7

Enrolled (actual)
203
Serious AEs
44.5%
Results posted
May 2021
Primary outcome: Primary: Disease-free Survival (DFS) — 19.6; 14.2 months — p=0.85

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Carboplatin (Drug); Laboratory Biomarker Analysis (Other); Paclitaxel (Drug); Quality-of-Life Assessment (Other); Radiation Therapy (Radiation); Therapeutic Conventional Surgery (Procedure); Trastuzumab (Biological)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
National Cancer Institute (NCI)
Primary completion
Dec 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Disease-free Survival (DFS)
19.6; 14.2 0.85
SECONDARY
Percentage of Participants With Pathologic Complete Response at Surgery
27; 29 0.71
SECONDARY
Overall Survival
38.5; 38.9 0.95
SECONDARY
Frequency of Highest Grade Adverse Event Per Participant
0; 0; 14; 12; 49; 56
SECONDARY
Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment
46; 38; 39; 42; 41; 27 0.39
SECONDARY
Quality-adjusted Survival
SECONDARY
Molecular Correlates of Efficacy
SECONDARY
Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
30; 24 0.021 sig

Summary

This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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 spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

Eligibility Criteria

Inclusion Criteria

  • Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm
  • Endoscopy with biopsy
  • PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION
  • Intent to submit tissue for central HER2 testing
  • Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up:
  • Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing)
  • Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be = = 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Creatinine = = institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration
  • Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab

Exclusion Criteria

  • Patients with cervical esophageal carcinoma
  • Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
  • Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiation therapy for esophageal cancer or prior chest radiotherapy
  • Prior anthracycline or taxane
  • Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
  • Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)
  • Medical contraindications to esophagectomy
  • Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor [EGFR]) pathway
  • Prior therapy with trastuzumab
  • Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
  • Previous history of congestive heart failure
  • Severe, active comorbidity, defined as follows:
  • Unstable angina in the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • 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; protocol-specific requirements may also exclude immunocompromised patients
  • Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01196390). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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