BrUOG 413: A Phase II Study of Adjuvant Trastuzumab Deruxtecan (Enhertu) + Nivolumab For Patients Who Are Disease Free After Completion of Trimodality Treatment For HER-2-Positive Cancers of the Esophagus and Gastroesophageal Junction
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Esophageal Adenocarcinoma
- Sponsor
- Brown University
- Enrollment
- 1
- Locations
- 4
- Primary Endpoint
- Safety of the addition of adjuvant trastuzumab deruxtecan with nivolumab for patients with esophagogastric cancer who have completed trimodality treatment
- Status
- Active, not recruiting
- Last Updated
- 11 days ago
Overview
Brief Summary
An open label phase II study to determine the safety and preliminary efficacy of the combination of 1-year of adjuvant trastuzumab deruxtecan and nivolumab for patients with HER2 overexpressing esophagogastric adenocarcinoma who have completed chemoradiation followed by esophagectomy.
Detailed Description
This is an open label phase II study to determine the safety and preliminary efficacy of the combination of 1-year of adjuvant trastuzumab deruxtecan and nivolumab for patients with HER2 overexpressing esophagogastric adenocarcinoma who have completed chemoradiation followed by esophagectomy. All patients will receive trastuzumab deruxtecan, 6.4 mg/kg IV, and nivolumab, 360 mg IV, every 21 days, for 17 doses over 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed primary adenocarcinoma of the esophagus, esophagogastric junction or (Stomach involvement is allowed.).
- •HER2 overexpression defined by immunohistochemistry (IHC) 3+ or HER2 amplification by fluorescence in situ hybridization (FISH). This may be defined by local or commercial laboratories
- •Completed trimodality treatment with chemoradiation followed by esophagectomy and had an R0 resection but did not achieve a complete pathologic response.
- •4 - 12 weeks after esophagectomy.
- •Prior to trimodality treatment had stage T1N1-2 M0, T2-3N0-2 M0 disease.
- •ECOG performance status 0-1
- •For women of childbearing potential, a negative serum pregnancy test within 7 days prior to registration
- •Women of childbearing potential and male participants must practice highly effective form of non-hormonal contraception throughout the study, which is defined as from study screening (ICF) through 2 months post last treatment; Non-sterilised male partners of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period.
- •Ability to understand and the willingness to sign a written informed consent document.
- •LVEF ≥ 50% within 28 days before randomization/enrollment.
Exclusion Criteria
- •Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
- •Patients with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
- •Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \>450 msec (males) based on average of the screening triplicate12-lead ECG.
- •History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
- •History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)
- •Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
- •Prior pneumonectomy (complete)
- •Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- •Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day
Arms & Interventions
Starting Trastuzumab Deruxtecan Dose
Trastuzumab deruxtecan, 6.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Nivolumab
Starting Trastuzumab Deruxtecan Dose
Trastuzumab deruxtecan, 6.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Trastuzumab deruxtecan
First Trastuzumab Deruxtecan Dose Reduction
Trastuzumab deruxtecan, 5.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Nivolumab
Second Trastuzumab Deruxtecan Dose Reduction
Trastuzumab deruxtecan, 4.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Nivolumab
First Trastuzumab Deruxtecan Dose Reduction
Trastuzumab deruxtecan, 5.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Trastuzumab deruxtecan
Second Trastuzumab Deruxtecan Dose Reduction
Trastuzumab deruxtecan, 4.4 mg/kg IV every 3 weeks for 17 doses (12 months)
Intervention: Trastuzumab deruxtecan
Outcomes
Primary Outcomes
Safety of the addition of adjuvant trastuzumab deruxtecan with nivolumab for patients with esophagogastric cancer who have completed trimodality treatment
Time Frame: First dose of study treatment, through 30-days post last dose of drug, approximately 13 months
Measured by the rates of clinically significant treatment-related grade ≥3 adverse events or pneumonitis.
Secondary Outcomes
- Disease-free survival with adjuvant trastuzumab deruxtecan & nivolumab after completion of trimodality treatment for HER2+ esophageal cancer.(First dose of study treatment until time of cancer recurrence or death from any cause, whichever occurs first, maximum of 36 months)