Clinical trial: KD019 and Trastuzumab in Patients With Esophagus, Gastroesophageal Junction and Stomach Cancer (NCT02205463)

Eligibility criteria:
Inclusion Criteria:

        Patients must meet all of the following inclusion criteria to be eligible for enrollment
        into the study:

          -  Pathologically confirmed diagnosis of adenocarcinoma of stomach, GEJ or esophagus
             (central confirmation is not required). Primary tumor or metastatic lesion must be
             HER2+ documented as HER2 gene amplification by FISH as positive (HER2:CEP17 ratio of
             ≥2.0) or IHC 3+.

          -  Metastatic or unresectable adenocarcinoma of stomach, GEJ, or esophagus that is
             evaluable or that is measurable for response as per RECIST 1.1 criteria, defined as at
             least one lesion that can be accurately measured in at least one dimension (longest
             diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with
             spiral computed tomography (CT) scan.

          -  Adult subjects greater than 18 years of age

          -  Patients who received postoperative adjuvant therapy with a single-agent
             fluoropyrimidine and radiation are eligible.

          -  Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

          -  Adequate organ and bone marrow functions defined as follows:

        oAbsolute neutrophil count >1,500 cells/ul

          -  Platelets >100,000/ul

          -  Hemoglobin >9.0g/dl

          -  INR < or equal to 1.5 or INR < or equal to 3 if patient is on warfarin

          -  Serum creatinine < or equal to 1.5 times upper limit of normal (ULN) or calculated
             creatinine clearance (CRCL) > or equal to 60ml/min

          -  Serum electrolytes within the normal range (per institution standard) during
             screening.

          -  Total bilirubin less than or equal to 1.5 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or equal to 3
             times ULN

          -  Albumin > or equal to 3g/dL

               -  No history of another malignancy in the past 5 years, except treated non-melanoma
                  skin cancer or superficial bladder cancer or carcinoma-in-situ of the cervix

               -  No coexisting medical problems of sufficient severity to limit compliance with
                  the study

               -  Ability to understand and sign a written informed consent document. Patient must
                  have willingness and ability to comply with scheduled visits, treatment plans,
                  laboratory tests and other study procedures.

               -  Female subjects of childbearing potential must have a negative serum pregnancy
                  test prior to study entry (positive urine tests are to be confirmed by serum
                  test).

               -  Female subjects of childbearing potential and males must agree to use a highly
                  effective method of contraception (<1% per year failure rate) for the duration of
                  study treatment and for six months after discontinuation of the study drug.
                  Highly effective birth control methods include implants, injectables, combined
                  oral contraceptives, some IUDs, sexual abstinence, or vasectomy for males.

        Exclusion Criteria:

          -  Prior treatment chemotherapy or HER2-directed therapy for metastatic gastric, GEJ or
             esophageal adenocarcinoma chemotherapy.

          -  Prior peri-operative therapy with a platinum-containing regimen.

          -  Angina secondary to fluoropyrimidine therapy in the adjuvant setting

          -  Surgery, radiotherapy, or lesion ablative procedure to the only area of
             measurable/evaluable disease.

          -  Major surgery within 4 weeks prior to the first dose of KD019

          -  Left ventricular ejection fraction (EF) <50% at baseline as measured by multi-gated
             acquisition (MUGA) scan or echocardiogram (ECHO).

          -  Treatment with chronic immunosuppressants (e.g. cyclosporine following
             transplantation)

          -  Current known active infection with HIV, hepatitis B or C viruses

          -  Uncontrolled systemic disease

          -  Brain metastases that are:

               -  Untreated or

               -  Progressive or

               -  Have required any type of therapy (including radiation, surgery, steroids or
                  anticonvulsant therapy) to control symptoms from brain metastases within 60 days
                  prior to the first study treatment

               -  Leptomeningeal

               -  Hemorrhagic

          -  Subject has evidence of pre-existing idiopathic pulmonary fibrosis on CT scan at
             baseline

          -  History of an invasive secondary primary malignancy diagnosed within the previous 3
             years, except for appropriately treated stage I endometrial or cervical carcinoma,
             prostate carcinoma treated surgically or non-melanoma skin cancer.

          -  No other non-protocol antineoplastic agents will be permitted during this study

          -  Patients may not be receiving any other investigational agents.

          -  Women who are pregnant or lactating.

          -  Subject has any of the following EKG criteria:

               -  Corrected QT interval (QTc) of >0.47 seconds

               -  Finding of a left bundle branch block or right bundle bunch block

          -  Bradycardia defined as a heart rate of <50 beats per minute (bpm)

          -  Presence of a pacemaker or implantable cardioverter defibrillator (ICD)

          -  History of sustained ventricular arrhythmias (subjects with a history of atrial
             arrhythmias should be discussed with the sponsor before entry into the study)

          -  Family history of congenital long QT syndrome or unexplained sudden death.

          -  Moderate or severe pulmonary dysfunction

          -  History of clinically significant cardiac dysfunction including:

               -  Unstable angina

               -  History of myocardial infarction (MI) within 6 months prior to first study
                  treatment

               -  History of symptomatic CHF (grade >3 by NCI CTCAE or Class >II by New York Heart
                  Association (NYHA) criteria or serious cardiac arrhythmia requiring treatment,
                  with the exception of atrial fibrillation and paroxysmal supraventricular
                  tachycardia

               -  Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 160 and/or
                  diastolic blood pressure (DBP) ≥ 100 despite maximal medical therapy.

          -  Subject requires treatment with drugs known to be associated with torsades de pointes
             or significant QT interval prolongation.

               -  Patients will be eligible for the study if they discontinue any medications
                  listed in one week prior to registration and study enrollment.

               -  Stable regimen of antidepressants of the SSRI class is allowed (common SSRIs
                  include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline and
                  fluoxetine)

          -  Use of cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin,
             carbamazepine or phenobarbital) is not allowed.

          -  Subject has a serum potassium or magnesium level outside the normal range despite
             repletion.

          -  Has gastrointestinal tract disease resulting in an inability to take or absorb oral
             medication.

          -  Inclusion or exclusion of patients on other medications, or severe acute/chronic
             medical or psychiatric conditions or laboratory abnormality that may increase the risk
             associated with study participation or study drug administration, or may interfere
             with the interpretation of study results will be at the judgment of the study
             investigator.

          -  Subject is unable or unwilling to abide by the study protocol or cooperate fully with
             the investigator or designee.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient description (patient's own words): I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Does the patient match the trial criteria? Entailment