Clinical trial: A Phase II Trial of iTTo in Advanced Gastric and GEJ Adenocarcinoma (NCT04808791)

Eligibility criteria:
Inclusion Criteria:

          1. Patients must be 18 years of age or older.

          2. Histologically documented locally advanced or metastatic gastric or GEJ adenocarcinoma
             not previously treated with palliative systemic therapy.

          3. Patients must be capable of providing consent to enrolment and treatment.

          4. Patients with a performance status of ECOG 0-1 will be eligible for enrolment (see
             appendix 1).

          5. Measurable disease must be present according to RECIST criteria V1.1 (see appendix ).

          6. Women of child bearing potential (WOCBP) must have a negative serum (or urine)
             pregnancy test at the time of screening. WOCBP is defined as any female who has
             experienced menarche and who has not undergone surgical sterilization (hysterectomy or
             bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal.
             Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the
             absence of other biological or physiological causes.

          7. Patients (men and women) of childbearing / reproductive potential should use highly
             effective birth control methods, as defined by the investigator, during the study
             treatment period and for a period of 6 months after the last dose of study drug. A
             highly effective method of birth control is defined as those that result in low
             failure rate (i.e. less than 1% per year) when used consistently and correctly. Note:
             abstinence is acceptable if this is established and preferred contraception for the
             patient and is accepted as a local standard.

          8. Female patients who are breast-feeding should discontinue nursing prior to the first
             dose of study treatment and until 30 days after the last dose of study drug.

          9. Male patients should agree to not donate sperm during the study and for a period of at
             least 6 months after last dose of study drug.

         10. Absence of any condition hampering compliance with the study protocol and follow- up
             schedule; those conditions should be discussed with the patient before registration in
             the trial.

         11. Patients may have received prior surgery if this surgery was ≥ 4 weeks before study
             entry and patients must have recovered from the toxic effects of this treatment.

         12. Patients who have treated brain metastasis (via local radiation standards or surgical
             resection or local ablative techniques) and who are either off steroids or on a stable
             dose of steroids for at least one month (30 days), AND who are off anticonvulsants,
             AND have radiological documented stability of lesions for at least 3 months may be
             eligible. Each case should be discussed with the study Chair.

         13. Patients who have received prior chemotherapy or radiation delivered as part of
             initial curative therapy (i.e. neoadjuvant or adjuvant chemotherapy administered alone
             and/or concurrently delivered with radiation and/or surgery) are permitted as long as
             that treatment was completed at least 6 months prior to study start date.

         14. Patients may have received prior palliative radiotherapy (unless radiation was
             curative therapy to pelvis or to ≥ 25% of bone marrow stores) if this radiation was ≥
             4 weeks before study entry and patients must have recovered from the toxic effects of
             this treatment.

         15. Patients with unknown Her2/neu status, or negative Her2/neu status based on IHC and/or
             FISH/CISH (Testing does not need to be done unless it is standard of care at
             participating centres).

         16. The following adequate organ function laboratory values must be met:

        Hematological:

        Absolute neutrophil count (ANC) >1.5 x10^9/L Platelet count >100 x10^9/L Hemoglobin >8 g/dL
        (may have been transfused)

        Renal:

        serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance
        of ≥ 50 mL/min using the Cockcroft-Gault formula (or local institutional standard method)

        Hepatic:

        Total serum bilirubin <1.5x ULN AST and ALT <2.5x ULN (or ≤ 5 x ULN for patients with
        documented metastatic disease to the liver)

        Exclusion Criteria:

          1. Patients who have received prior palliative chemotherapy for their advanced gastric or
             GEJ tumor.

          2. Prior curative or palliative radiation treatment to the pelvis or radiation therapy to
             ≥ 25% of bone marrow stores.

          3. History of bowel obstruction due to peritoneal metastases or clinically documented
             ascites requiring paracenteses.

          4. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of
             the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate
             (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment,
             unless at least 5 years have elapsed since last treatment and the patient is
             considered cured).

          5. Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as
             ongoing signs/symptoms related to the infection without improvement despite
             appropriate antibiotics, antiviral therapy, and/or other treatment.

          6. Known infection with hepatitis B or C, or history of human immunodeficiency virus
             (HIV) infection, or subject receiving immunosuppressive or myelosuppressive
             medications that would, in the opinion of the investigator, increase the risk of
             serious neutropenic complications.

          7. Any serious medical condition within 6 months prior to study entry such as myocardial
             infarction, uncontrolled congestive heart failure, unstable angina, active
             cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases,
             uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder,
             serious infection, active peptic ulcer disease, or other medical condition that may be
             aggravated by treatment.

          8. Pre-existing neuropathy ≥ grade 2 from any cause.

          9. Patients with unstable metastasis to the central nervous system (CNS). A CT scan or
             MRI is NOT required to rule out brain metastases unless there is clinical suspicion of
             CNS involvement.

         10. Pregnant or lactating women; women of child bearing potential must have a negative
             serum pregnancy test within 7 days of trial registration. Women or men of child
             bearing potential must use effective contraception (defined by the treating physician)
             which must be documented in study CRFs.

         11. History of allergic reaction to planned study medications.

         12. Patient has a ≥ 20% decrease in serum albumin level between baseline visit, if
             available, and within 72 hours prior to first study treatment dose.

         13. Patient is on coumadin.

         14. History of interstitial lung disease.

         15. History of connective tissue disorders (e.g. lupus, scleroderma, polyarteritis
             nodosa).

         16. Enrollment in any other clinical protocol or investigational study with an
             interventional agent or assessments that may interfere with study procedures.

         17. Any significant medical condition, laboratory abnormality, or psychiatric illness,
             that would prevent the subject from participating in the study, places the subject at
             unacceptable risk if he/she were to participate in the study, or any condition that
             confounds the ability to interpret data from the study.

         18. Positive Her2/neu status (NOTE: if this is discovered after patient has already been
             enrolled on study, patient may continue on study per the discretion of the treating
             physician.)
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