Molecular Profile-Directed Chemotherapy in Treating Patients with Metastatic HER2 Negative Esophagogastric Cancer
This pilot clinical trial studies molecular profile-directed chemotherapy (otherwise known as personalized treatment) in treating patients with human epidermal growth factor receptor 2 (HER2) negative esophagogastric cancer that has spread to other places in the body. Drugs used in chemotherapy 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. Studying the genes in a patient’s tumor cells may help doctors plan the most effective treatment.
Inclusion Criteria
- Patients with advanced, measurable metastatic EGA, by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- Patients who have had surgery or radiotherapy with or without neoadjuvant or adjuvant chemotherapy (the wash-out period will be at least 1 month)
- Patients who are not eligible for resection and are chemotherapy naïve
- Patients with HER2(-) status
- Patients who have tumor deposit(s) that are easily accessible by ultrasound or computed tomography (CT) guidance will be eligible for study; this is the case even in the event that a qualifying archived tumor sample is already available for a particular patient―qualifying archived tumor tissue is tissue extracted while the patient was in the same untreated state as when screened (usually tissue taken within 8 weeks prior to screening)
- Total bilirubin < 3 the upper limit of normal (ULN), except patients who are assigned to receive docetaxel must have liver function tests (serum transaminases, bilirubin) that are within 1.5 x the ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x ULN, except patients who are assigned to receive docetaxel must have liver function tests (serum transaminases, bilirubin) that are within 1.5 x the ULN
- Creatinine less than 1.5 x ULN, or a 24 hour creatinine clearance of 60 mg/mL or more
- Hemoglobin > 8.0
- Platelet > 100
- White blood cells (WBC) > 3.0
- Patients must provide written informed consent
- Physician recruitment will consist of surveying the physicians involved in treating patients on this pilot study; physician participation will be voluntary; physicians will indicate their consent through completion of the survey; survey instructions will include information about the voluntary nature of participation, confidentiality of responses and the minimal risk related to involvement
Exclusion Criteria
- Patients with active concurrent malignancy, other than superficial, non-invasive squamous cell carcinoma of the skin or uterine cervix, within the past three years
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status worse than 2 (ie unable to perform their own activities of daily living [ADLs] without assistance, unable to spend less than 50% of day out of bed)
- Patients with prior oral or intravenous chemotherapy for metastatic disease * Patients may have had adjuvant or neoadjuvant chemotherapy, if therapy was completed more than 6 months prior to enrollment * Patients whose comorbidities prevent them from being able to receive the designated chemotherapy regimen * Patients who are assigned to receive epirubicin must have cardiac ejection fraction (EF) of 45% or greater
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02358863.
PRIMARY OBJECTIVES:
I. To determine the estimates of outcomes necessary to plan and conduct subsequent studies with Molecular Profile-Directed therapy, for patients with metastatic esophagogastric adenocarcinoma (mEGA): Outcomes will include the timing of establishing the molecular profile, the proportion of patients with meaningful profiles, adverse events, and the objective response rate (ORR) overall.
SECONDARY OBJECTIVES:
I. To estimate in patients with mEGA, treated with Molecular Profile-Directed therapy, the: disease control rate (DCR = complete response [CR] + partial response [PR] + stable disease [SD] at 6 months); progression-free survival (PFS); overall survival (OS); time to disease progression (TTP); duration of disease control (DDC).
TERTIARY OBJECTIVES:
I. To examine molecular markers of chemotherapy response.
II. To analyze all patient molecular results to determine if common patterns emerge that could inform future trial design.
III. To assess physician attitudes toward and treatment decisions related to molecular profile results from patient tumors. Outcomes will include: perceived facilitators and barriers that impact decisions to use treatment based on molecular tumor profiles; perceived importance of using molecular tumor profile information in cancer care; acceptability of using molecular tumor profile results in treatment decision making.
IV. To assess patients’ quality of life outcomes.
OUTLINE: Patients are assigned to 1 of 11 treatment groups based on their molecular profile.
ARM I: Patients receive oxaliplatin intravenously (IV), leucovorin calcium IV, and fluorouracil IV over 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive docetaxel IV on days 1 and 8 and capecitabine orally (PO) twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive cisplatin IV and irinotecan hydrochloride IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients receive cisplatin IV and docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM V: Patients receive irinotecan hydrochloride IV over 90 minutes and epirubicin hydrochloride IV over 10-15 minutes on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM VI: Patients receive docetaxel IV on day 1 and epirubicin hydrochloride IV on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM VII: Patients receive irinotecan hydrochloride IV and docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM VIII: Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM IX: Patients receive irinotecan hydrochloride IV, leucovorin calcium IV, and fluorouracil IV on 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
ARM X: Patients receive cisplatin IV on day 1 and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM XI: Patients receive epirubicin hydrochloride IV on day 1 and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 12 months.
Trial PhasePhase O
Trial Typetreatment
Lead OrganizationMedStar Georgetown University Hospital
Principal InvestigatorJohn Lindsay Marshall
- Primary ID2013-0973
- Secondary IDsNCI-2014-02639
- ClinicalTrials.gov IDNCT02358863